bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigen-reactive T clones. III. Low responder antigen-presenting cells function effectively to present antigen to selected T cell clones derived from (High Responder x Low Responder)F1 mice.
Authors: Kimoto M , Krenz T J , Fathman C G
Published: June 2004

Long-term-cultured poly(Tyr, Glu)-poly-D,L,-Ala-poly-Lys [(T,G)-A--L]-reactive T cells and clones derived from (high responder x low responder)F1 [(C57BL/6 x A/J)F1] mice were shown to recognize (T,G)-A--L presented by cells from low responder strain A/J mice. The antigen-presenting determinant(s) that allowed recognition of (T,G)-A--L by such T cell clones was controlled by the I-A subregion of the major histocompatibility complex. These results suggest that there is no functional defect in the ability of low responder Ir gene products (I-A antigens) to associate with (T,G)-A--L for effective recognition by T cells. Although these results might tentatively be interpreted to suggest that Ir gene-controlled low responsiveness is due to the inability of the T cell to recognize the association between (T,G)-A--L and low responder I-A gene products, it is similarly possible that there might be a defect in the functional capabilities of low responder antigen-presenting cells to effectively process (T,G)-A--L into immunodominant epitopes.
T cell development. Precursors and inducer requirements of helper effector and feedback suppression inducer cell sets.
Authors: Shen F W , McDougal J S , Bard J , Cort S P
Published: June 2004

The surface phenotypes and differentiative history of specific helper-effector (HE) and specific feedback suppression-inducer (FBSI) cell sets were further defined in reference to the Qa-1 and I-J marker systems by culture of selected sets of cortisone-resistant nylon-purified thymocytes with antigen on primed macrophages. The generation of Ly-1:HE and Ly-1:FBSI cell sets required, in each case, two initiating sets: a precursor set and a differentiation-inducing set. Precursor sets were distinguished from inducer sets by genetic markers. Accordingly, HE cells, phenotype Ly-1:Qa-1-:I-J-, differentiated from Ly-123:Qa-1- cells in the presence of Ly-1:Qa-1+:I-J+ inducer cells; and FBSI cells, phenotype Ly-1:Qa-1+:I-J+, differentiated from Ly-123:Qa-1- in the presence of Ly-1:Qa-1+:I-J+ inducer cells. The Ly-123:Qa-1-precursors of HE and FBSI cells have been distinguished from one another previously but there is as yet no evidence whether differentiation of these precursor sets requires the same or different Ly-1:Qa-1+:I-J+ inducer sets.
Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2- lymphocytes.
Authors: Greenberg P D , Cheever M A , Fefer A
Published: June 2004

The phenotype of T cells therapeutically effective in immunotherapy of advanced Friend virus-induced (FBL) leukemia in vivo and cytotoxic to FBL in vitro was determined. Mice bearing disseminated FBL leukemia were successfully treated by a combination of cyclophosphamide and adoptive transfer of syngeneic immune lymphocytes. Therapeutic efficacy was largely dependent on the presence of Lyt-1+2- T cells in the transferred cells, whereas cells cytotoxic to FBL tumor in vitro were derived from the Lyt-1+2+ and Lyt-1-2+ subsets. Thus, the predominate cell required to eradicate tumor in adoptive chemoimmunotherapy was not cytolytic to tumor in vitro. Potentially, the Lyt-1+2- cell may operate in vivo as an amplifier cell rather than by a direct anti-tumor effect. Elimination of the Lyt-1+ population with alpha-Lyt-1 and complement prevented the generation of significant cytotoxic responses during both primary in vitro sensitization to alloantigens and in vitro sensitization of tumour-primed cells. The capacity of Lyt-1+ cell-depleted population to generate cytotoxic responses was partially reconstituted by addition, at the initiation of culture, of interluekin 2, a T cell growth factor derived from Lyt-1+2- cells, which contain the CTL and CTL precursors, were nearly as effective in vitro as unseparated immune cells. If the remaining effector cells (i.e., Lyt-1+2- T cells) function in vivo predominantly as amplifier cells, than the tumour-bearing host must be capable of making a positive contribution to the outcome of therapy.
Responder T cells depleted of alloreactive cells react to antigen presented on allogeneic macrophages from nonresponder strains.
Authors: Ishii N , Baxevanis C N , Nagy Z A , Klein J
Published: June 2004

T cells from strains responder to the antigen poly(Glu40 Ala60) (GA) were depleted of alloreactive cells by bromo-deoxyuridine and light treatment, and were subsequently primed in vitro in GA presented by allogeneic macrophages from nonresponder strains. Antigen-specific secondary proliferative responses restricted by allogeneic Ia molecules of the macrophages were obtained in all strain combinations tested. These data indicate that Ir gene-controlled nonresponsiveness cannot be the result of a failure of antigen presentation.
T cell-mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases.
Authors: Dye E S , North R J
Published: June 2004

Progressive growth of the P815 mastocytoma in semisyngeneic mice evokes the generation of a T cell-mediated mechanism of immunosuppression that inhibits the capacity of passively transferred, tumor-sensitized T cells from regressing this tumor in recipient mice. This conclusion is based on two findings: (a) that it is possible to demonstrate adoptive T cell-mediated regression of established tumors, but only if the tumors are growing in T cell-deficient recipients, and (b) that adoptive T cell-mediated regression of tumors in these recipients can be inhibited by the infusion of splenic T cells from T cell-intact, tumor-bearing donors. The results of additional experiments designed to measure the effect of decreasing the number of suppressor cells and the time that they are infused, relative immune cells, indicate that the function of suppressor cells in this model is to inhibit the replication of passively transferred immune T cells. The results obtained with the P815 mastocytoma are similar to those obtained previously with a chemically induced fibrosarcoma. They show, in addition, that passively transferred immune cells are capable of destroying already seeded metastases in T cell-deficient recipients.
Fibronectin and C4-binding protein are selectively bound by aggregated amyloid P component
Authors: DeBeer FC , Baltz ML , Holford S , Feinstein A , Pepys MB
Published: June 2004

Serum amyloid P component (SAP) is a normal plasma protein, closely related to C-reactive protein, which is deposited together with amyloid fibrils in all forms of amyloidosis. It is also a normal constituent of human tissues, where it is found in vascular basement membranes and in association with the peripheral microfibrillar mantle of elastic fibres throughout the body. Very similar, highly conserved, homologous proteins are present in the sera of all vertebrates in which they have been sought, and in all cases these proteins display calcium-dependent binding affinity for agarose. The physiological function or pathogenetic significance of this reactivity are not known but we report here for the first time that under appropriate conditions human SAP can also bind certain serum glycoproteins. SAP, which had been aggregated either by direct conjugation to CNBr-activated Sepharose beads, or by complexing with anti-SAP antibodies immobilized on such beads, selectively took up fibronectin and C4-binding protein from whole normal human serum. The reaction was calcium dependent and the two ligands were bound independently of each other or of other serum constituents. Experiments with isolated fibronectin and SAP complexed by anti-SAP-Sepharose indicated that close association of pairs of SAP molecules was required for fibronectin to be bound and that each SAP dimer was capable of taking up a single molecule of fibronectin. There was no evidence that SAP in its native state in the serum was complexed with either fibronectin or C4-binding protein. The present findings significantly extend knowledge of the properties of SAP and open the way to characterisation of its physiological ligand(s) and thence to elucidation of its function.
Cellular interactions in immune regulation. Hapten-specific suppression by non-T cells and T cell-mediated reversal of suppression
Authors: DeKruyff RH , Simonson BG , Siskind GW
Published: June 2004

The ability of lymphoid cells from immunized animals to regulate the response of naive B ceils to the immunizing hapten was studied. Mice were immunized with trinitrophenylated (TNP) bovine gamma globulin (BGG) in complete Freund's adjuvant, and their spleen cells were examined in vivo and in vitro for the presence of specific inhibitory activity. This activity was found to peak 1 wk after immunization, was active against TNP on both T-dependent (BGG) and T-independent (Ficoll and polyacrylamide beads) carriers, and was demonstrable both by mixed cell transfers and mixed cell culture experiments. In in vitro studies, it was shown that the inhibition of the response to TNP- polyacrylamide beads by immune spleen cells was mediated by a non-T cell, possibly a B cell, because the suppressor activity was enriched in a purified B cell preparation. A role for macrophages was not formally ruled out. A specific suppressor factor was produced in vitro by immune spleen cells cultured in the absence of antigen. The suppressor activity was modulated by T .cells because elimination of T cells from the normal spleen cell population decreased suppression; elimination of T cells from the immune spleen cell population did not effect suppression, but elimination of T cells from both the normal and immune spleen cell populations allowed the expression of marked specific suppression. Thus, T cells present in the normal spleen cell population augment the degree of suppression, whereas T cells present in the immune spleen cell population decrease the degree of suppression; that is, T cells present in the immune spleen cell population had the ability to specifically abrogate suppression ("abrosuppression") in a T-independent immune response. It is proposed that the response to a T- independent antigen is regulated by specific suppressor activity generated by a non-T cell and augmented by the interaction of this cell with a T cell. The suppressor activity can be blocked by a specific abrosuppressor T cell. It is suggested that, because suppressor activity appears dominant in the naive state of the immune system, the induction of specific abrosuppressor activity may be essential if an immune response is to take place.
Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex.
Authors: Colle E , Guttmann R D , Seemayer T
Published: June 2004

A syndrome of spontaneous diabetes mellitus has been previously described in a partially inbred rat strain called BB Wistar. We have determined whether there is major histocompatibility complex (MHC) linkage as well as other predisposing haplotype-associated factors of development. BB rats are RT1 (MHC) genotype u/u. Using BB x Lewis F1 hybrid matings, an F2 study analyzed 128 rats from 8 primary and 3 additional litters from a breeding pair producing a diabetic offspring. 4 of 128 F2 rats, all from the 48 progeny of same breeding pair, became clinically diabetic. The four diabetics were all genotype u/u (P = 0.03). In the primary F2 litters, haplotype distribution was not different from the 1:2:1 expected ratio. However, in the four litters from the from the F1 breeding pair producing diabetics, there was an increased number of u/u animals. Two-way analysis of variance revealed significant differences in pancreatic insulin content between litters (diabetics excluded), P less than 0.001, and between haplotypes P less than 0.007 with heterozygous u/u less than 1/1 progeny. The glucagon content showed no significant differences. These data demonstrate (a) MHC linkage with spontaneous diabetes in this rat model; (b) penetrance similar to the human disease; and (c) a possible association of MHC haplotype with pancreatic inflammation as well as insulin content in nondiabetic F2 siblings.
T cell receptors with allo-major histocompatibility complex specificity from rat and mouse. Similarity of size, plasmin susceptibility, and localization of antigen-binding region.
Authors: Binz H , Wigzell H
Published: June 2004

Antisera specific for the constant part Ctau of T cell receptor molecules in mice and rats have been produced in rabbits by immunization with idiotype-positive rat T cell molecules. Such antisera could be shown to react with the majority of normal T lymphocytes from both rats and mice. Mixed leukocyte culture-activated T blasts displayed a higher percentage of positive cells than concanovalin A- or phytohemaglutinin-induced T blasts. Lipopolysaccharide-induced B blasts were not reactive with the antiserum. Lyt-1-,2+,3+ blasts displayed a significantly brighter straining than the corresponding Lyt-1+,2-,3- blasts. Isolation of the reactive molecules from T cells by immunosorption yielded a 70,000-dalton single chain polypeptide as the dominant group of molecules. Plasmin caused the chain to split into 45,000- and 25,000-dalton polypeptides, with the smaller fragment displaying antigen-binding capacity. Molecules identical in size and plasma degradation patterns were isolated from Lyt-1+,2-3- and 1-,2+,3+ blasts. Preliminary functional data supported the view that the antiserum is directed against the constant region Ctau relevant receptor structures on immunocompetent T lymphocytes.
Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XII. Fine specificity of anti-idiotypic suppressor T cells (Ts2).
Authors: Sherr D H , Ju S T , Dorf M E
Published: June 2004

The fine specificity of anti-idiotypic, effector-phase suppressor T cells (Ts2) induced by the intravenous injection of syngeneic spleen cells covalently coupled with the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten was studied in an in vitro plaque-forming cell system. By comparing the ability of these suppressor cells to bind monoclonal anti-NP antibodies that express different levels of serologically detected NPb idiotypic determinants, it was shown that anti-idiotypic suppressor T cells do not recognize the predominant NPb idiotypic determinants that are defined by serologic analysis. The implications for the possible expression and/or recognition of different sets of idiotypic determinants on T and B cells are discussed.
Analysis of T cell hybridomas. I. Characterization of H-2 and Igh-restricted monoclonal suppressor factors.
Authors: Minami M , Okuda K , Furusawa S , Benacerraf B , Dorf M E
Published: June 2004

Five hybridoma T cell lines were prepared by fusion of second order suppressor T cells (Ts2) with the BW5147 thymoma. The culture supernates from these T cell hybrids contained a factor, TsF2, which specifically suppressed 4-hydroxy-3-nitrophenyl acetyl hapten (NP)-induced cutaneous sensitivity responses. TsF2 activity was observed when the factor was administered during the effector phases of the immune response. TsF2 bears I-J determinants and has binding specificity for NPb idiotypic determinants. TsF2 suppressor activity could be absorbed on antigen-primed H-2-incompatible T cells but cannot suppress H-2-incompatible mice. In addition to this H-2 restriction, which maps to the I-J subregion, monoclonal TsF2 also has an Igh genetic restriction. The present results are combined with previous data to describe the cellular interactions leading to immune suppression.
Major histocompatibility complex-restricted antigen presentation to antigen-reactive T cells by B lymphocyte tumor cells.
Authors: McKean D J , Infante A J , Nilson A , Kimoto M , Fathman C G , Walker E , Warner N
Published: June 2004

Previous reports have demonstrated that accessory cells function to present soluble protein antigens in association with gene products encoded within the I region of the major histocompatibility complex (MHC) to antigen-reactive T helper cells. The biochemical events that occur during antigen presentation are, however, not well-documented primarily because of the difficulties involved in purifying sufficient numbers of homogeneous antigen-presenting cells. In this paper, a number of Ia-positive B lymphocyte tumor lines are shown to be capable of presenting soluble protein antigens to antigen-reactive continuous T cell lines in an MHC-restricted fashion. The characterization of the antigen presentation function of these tumor cells indicates that the tumor cells have many of the functional antigen-presenting characteristics previously thought to be limited to macrophages. These tumor cells should provide a useful model system for determining the biochemical events that occur in antigen uptake and processing as well as for determining the potential interactions between processed antigen and Ia molecules on the plasma membrane of these antigen-presenting cells.
Expression of an idiotype (Id-460) during in vivo anti-dinitrophenyl antibody responses. III. Detection of Id-460 in normal serum that does not bind dinitrophenyl.
Authors: Dzierzak E A , Janeway C A
Published: June 2004

Using an anti-idiotypic antibody previously characterized as specific for the hapten binding site of the 2,4-dinitrophenyl (DNP)-binding BALB/c myeloma protein MOPC-460, we have detected substantial amounts of this idiotype (Id-460) in the serum of normal mice. Whereas the idiotypic material in DNP-immune serum binds to DNP, the Id-460-positive material in normal mouse serum is not specific for DNP. The material in normal serum appears to be immunoglobulin. Furthermore, Id-460-positive, non-DNP-binding monoclonal immunoglobulins that completely inhibit our assay for Id-460 are repeatedly isolated when hybridomas are prepared from LPS-activated normal spleen cells. These data are interpreted in the context of Jerne's network hypothesis. It is our conclusion that the non-DNP-binding form of Id-460 is the inherited form and that this form establishes an idiotypic network favoring the production of anti-DNP bearing Id-460. Thus, the paradox of finding an inherited idiotype in the antibody response to the nonpathogen DNP may be resolved by proposing that the true form of Id-460 is specific for an environmental pathogen and that Id-460 dominance in the anti-DNP response is simply a consequence of idiotype-specific regulatory events preconditioned by Id-460-bearing immunoglobulin specific for antigenic determinants unrelated to DNP.
Antitumor effects of hydrogen peroxide in vivo
Authors: Nathan CF , Cohn ZA
Published: June 2004

Glucose oxidase, covalently coupled to polystyrene microspheres (GOL), produced H(2)0(2) at an average rate of 3.6 nmol/min per 10(9) beads under standard assay conditions. Injection of 1.3 × 10(10) to 1.1 × 10(11) GOL i.p. prolonged the survival of mice by 27 percent after injection of 10(6) P388 lymphoma cells in the same site, consistent with destruction of 97.6 percent of the tumor cells. Placing mice for several hours in 100 percent O(2), the probable rate-limiting substrate for GOL, afforded a 42 percent prolongation of survival from P388 lymphoma, consistent with destruction of 99.6 percent of the tumor cells. When the P388 inoculum was 10(5), 10(4), or 10(3) cells, GOL led to long-term survival (presumed cure) of 23 percent, 77 percent, and 92 percent of the mice, respectively, consistent with reduction of the injected tumor dose to less than 10 cells. Subcutaneous growth of 10(5) P388 cells (approximately 300 lethal dose to 50 percent of mice) was suppressed in 83 percent of mice by admixture of GOL with the tumor cell inoculum. GOL alone had no effect against a more peroxide-resistant tumor, P815 mastocytoma. However, P815 cell glutathione reductase could be inhibited in vivo by well-tolerated doses of the antitumor agent, 1,3-bis(2-chloroethyl)- 1-nitrosourea (BCNU). BCNU alone cured few mice with P815. Together, BCNU and GOL apparently cured 86 percent of mice injected with 10(6) P815 cells i.p. The protective effect of GOL was abolished by boiling it to inactivate the enzyme, by co-injection of catalase coupled to latex beads, or by delaying the injection of tumor cells for 3 h, by which time the beads had formed aggregates. Soluble glucose oxidase, in doses threefold higher than that bound to GOL, had no detectable antitumor effect. A single injection of preformed H(2)0(2) readily killed P388 cells in the peritoneal cavity, but only at doses nearly lethal to the mice. In contrast, GOL had very little toxicity, as judged by the normal appearance of the mice for over 400 d, gross and microscopic findings at autopsy, and various blood tests. GOL injected i.p. remained in the peritoneal cavity, where it was gradually organized into granulomata by macrophages, without generalized inflammation. Thus, an H(2)0(2)-generating system confined to the tumor bed exerted clear- cut antitumor effects with little toxicity to the host.
Activated human monocytes inhibit the intracellular multiplication of legionnaires' disease bacteria
Authors: Horwitz MA , Silverstein SC
Published: June 2004

We have examined the interaction between virulent egg yolk-grown L. pneumophila, Philadelphia 1 strain, and in vitro-activated human monocytes, under antibiotic-free conditions. Freshly explanted human monocytes activated by incubation with concanavalin A (Con A) and human lymphocytes inhibited the intracellular multiplication of L. pneumophila. Both Con A and lymphocytes were required for activation. Con A was consistently maximally effective at greater than or equal to 4 μg/ml.

Monocytes activated by incubation with cell-free filtered supernatant from Con A-sensitized mononuclear cell cultures also inhibited the intracellular multiplication of L. pneumophil a. The most potent supernatant was obtained from mononuclear cell cultures incubated with greater than or equal to 15 μg/ml Con A for 48 h. The degree of monocyte inhibition of L. pneumophila multiplication was proportional to the length of time monocytes were preincubated with supernatant (48 {greater than} 24 {greater than} 12 h) and to the concentration of supernatant added (40 percent {greater than} 20 percent {greater than} 10 percent {greater than} 5 percent). Monocytes treated with supernatant daily were more inhibitory than monocytes treated initially only. With time in culture, monocytes progressively lost a limited degree of spontaneous inhibitory capacity and also lost their capacity to respond to supernatant with inhibition of L. pneumophila multiplication.

Supernatant-activated monocytes inhibited L. pneumophila multiplication in two ways. They phagocytosed fewer bacteria, and they slowed the rate of intracellular multiplication of bacteria that were internalized. As was the case with nonactivated monocytes, antibody had no effect on the rate of intracellular multiplication in supernatant-activated monocytes.

Neither supernatant-activated nor nonactivated monocytes killed L. pneumophila in the absence of antibody. Both killed a limited proportion of these bacteria in the presence of antibody and complement.

We have previously reported that anti-L, pneumophila antibody and complement neither promote effective killing of L. pneumophila by human polymorphonuclear leukocytes and monocytes nor inhibit the rate of L. pneumophila multiplication in monocytes. These findings and our present report that activated monocytes do inhibit L. pneumophila multiplication indicate that cell-mediated immunity plays a major role in host defense against Legionnaires' disease.
In vivo effects of antibodies to immune response gene products. I. Haplotype-specific suppression of humoral immune responses with a monoclonal anti-I-A.
Authors: Rosenbaum J T , Adelman N E , McDevitt H O
Published: June 2004

Immune response (Ir) gene products control immunologic function at several critical sites. We administered in vivo a monoclonal antibody reactive with I-Ak to F1 mice with the genotype H-2k/b. These treated mnice made a markedly reduced antibody response to antigen (H,G)-A--L, under the control of I-Ak, but not to antigen (T,G)-A--L, under the control of I-Ab. This relative specificity was lost if the antigen was given in complete Freund's adjuvant rather than aqueous solution. The monoclonal antibody reduced the antibody titer in an ongoing, secondary response as well. Several potential mechanisms can be postulated for this effect. This haplotypic specificity might ultimately be relevant to human disease.
C-reactive protein is protective against Streptococcus pneumoniae infection in mice.
Authors: Mold C , Nakayama S , Holzer T J , Gewurz H , Du Clos T W
Published: June 2004

C-reactive protein (CRP) has several properties that suggest that it may function as a bacterial opsonin. CRP shows binding reactivity with pneumococcal C-polysaccharide, the cell wall carbohydrate of Streptococcus pneumoniae. In this study we have demonstrated protection of mice against serotypes 3 and 4 of S. pneumoniae infection by a single prior injection of CRP. This effect was seen both in mice that lacked antibody to phosphocholine and in normal mice. Thus the opsonic properties of CRP previously described may be related to protection against pneumococcal infection.
Heterogeneity in surface antigen and glycoprotein expression of cell lines derived from different melanoma metastases of the same patient. Implications for the study of tumor antigens.
Authors: Albino A P , Lloyd K O , Houghton A N , Oettgen H F , Old L J
Published: June 2004

Three established lines of melanoma cells were derived from anatomically distinct metastases occurring in a single patient (DX). The lines, DX-1, DX-2, and DX-3, showed marked phenotypic diversity, as indicated by characteristic differences in growth rate, morphology, pigmentation, and the expression of surface antigens and glycoproteins. DX-1 and DX-3 expressed HLA-DR products, whereas DX-2 lacked HLA-DR expression. DX-1, DX-2, and DX-3 could also be distinguished on the basis of the profile of radiolabeled glycoproteins. Additional quantitative differences in the surface antigenic phenotype of the three cell lines were revealed by serological tests with a battery of monoclonal and conventional antibodies defining melanoma differentiation antigens. In tests for autologous humoral immunity to melanoma cells, sera from patient DX were found to have IgG antibody that reacted with surface antigens of DX-2 cells; no autologous reactivity was seen with DX-1 or DX-3 target cells or with three more recently established melanoma cell lines from patient DX. Absorption analysis indicated that the antigen detected by DX sera on DX-2 cells is a class 1 melanoma antigen, having been detected only on DX-2 cells and in much lower but demonstrable amounts on DX-1 and DX-3 cells. No other cell type, including DX normal fibroblasts, DX B cells, or 45 allogeneic melanoma cell lines expressed the class 1 antigen of DX melanoma. The fact that only one of the melanoma cell lines derived from patient DX was suitable target for the detection of autologous class 1 reactivity has implications for the study of human tumor antigens and may explain why antibody to class 1 antigens has been found so infrequently in past studies of melanoma patients.
A nuclear antigen associated with cell proliferation and blast transformation.
Authors: Takasaki Y , Deng J S , Tan E M
Published: June 2004

A nuclear antigen associated with cell proliferation (proliferating cell nuclear antigen-PCNA) and blast transformation is recognized by autoantibodies in the sera of some patients with systemic lupus erythematosus. This autoantibody is a precipitating antibody and also reacts in immunofluorescence, staining the nucleoplasm of proliferating and blast-transformed cells. The autoantibody was used as a reagent to determine the distribution of PCNA in a synchronized continuous B lymphoid cell line (WiL-2) and in mitogen-induced blast-transformed lymphocytes. In WiL-2 cells, PCNA was detected as speckled nucleoplasmic staining in G1, S, and G2 phases of the cell cycle. In addition, during late G1 and early S phases, PCNA was also detected in the nucleolus. During mitogen-induced blast transformation of lymphocytes, PCNA was noticed in the nucleolus before the initiation of DNA synthesis and later became nucleoplasmic with disappearance of nucleolar staining. These studies demonstrate that the relationship of PCNA to proliferation and blast transformation may be associated with events related to DNA synthesis in these cells.
Protection against graft vs. host-associated immunosuppression in F1 mice. I. Activation of F1 regulatory cells by host-specific anti-major histocompatibility complex antibodies.
Authors: Hurtenbach U , Sachs D H , Shearer G M
Published: June 2004

Injection of parental spleen cells into unirradiated F1 hybrid mice results in suppression of the potential to generate cytotoxic T lymphocyte (CTL) responses in vitro. In an attempt to protect the F1 mice from immunosuppression, the recipients were injected with antibodies specific for major histocompatibility complex (MHC)-encoded antigens of the F1 mice 24 h before inoculation of the parental spleen cells. 8-14 d later, the generation of CTL responses in vitro against H-2 alloantigens was tested. Alloantiserum directed against either parental haplotype of the F1 strain markedly diminished the suppression of CTL activity. Furthermore, monoclonal antibodies recognizing H-2 or Ia antigens protected the F2 mice from parental spleen cell-induced suppression. Although this study has been limited to reagents that recognize host H-2 determinants, these findings do not necessarily imply that protection against graft vs. host (GvH) can be achieved only with anti-MHC antibodies. However, protection was observed only by antibodies reactive with F1 antigens, and small amounts of the alloantibodies were sufficient to diminish CTL suppression. Adoptive transfer of spleen cells from syngeneic F1 mice treated with anti-h-2a alloantiserum 24 h previously provided protection equal to that of injection of the recipients with alloantibodies. The cells necessary for this effect were shown to be T cells and to be radiosensitive to 2000 rad. This cell population is induced by antisera against F1 cell surface antigens and effectively counteracts GvH-associated immuno-suppression.
Sex hormone regulation of in vitro immune response. Estradiol enhances human B cell maturation via inhibition of suppressor T cells in pokeweed mitogen-stimulated cultures.
Authors: Paavonen T , Andersson L C , Adlercreutz H
Published: June 2004

The effects of the main male and female sex hormones, testosterones and estradiol, in pokeweed mitogen (PWM)-stimulated cultures of human blood lymphocytes were studied. We found that the addition of physiological concentrations of estradiol (780-2,600 pmol/liter) to PWM cultures significantly increased the accumulation of immunoglobulin M-containing and -secreting cells detected by immunofluorescence and/or by the reversed protein-A plaque assay. The dose range of estradiol that induced enhanced B cell maturation did not affect the proliferative response. Estradiol displayed the same effect in vitro on lymphocytes from both men and women. Fractionation of lymphocyte subpopulations before culturing revealed that estradiol does not display a direct mitogenic or stimulatory effect of B cells. Instead, estradiol inhibits the suppressive activity of a radio-sensitive (1,000 rad) subset of T lymphocytes bearing Fc-receptors for immunoglobulin G. Nontoxic concentrations fo testosterone did not influence the in vitro B cell maturation. These observations provide a cellular basis for the differences in the immunoreactivities of males and females. The estradiol-induced inhibiton of suppressor T cells might be important for the pathogenesis of various autoimmune disorders.
The nature of the immunoglobulin G on the surface of B lymphocytes in chronic lymphocytic leukemia.
Authors: Stevenson F K , Hamblin T J , Stevenson G T
Published: June 2004

The nature of the immunoglobulin (Ig) G found associated with the neoplastic B lymphocytes in chronic lymphocytic leukemia that also express Igm and IgD had been investigated by absorption studies using anti-idiotypic antibodies raised against cell surface IgM from five patients. In all five cases, although cellular IgM and IgD behaved as idiotypic, the IgG did not. Thus the IgG frequently found associated with lymphocytes at this stage of differentiation is likely, at least in many cases, to be of extrinsic origin.
T cell clones with dual specificity for M1s and various major histocompatibility complex determinants.
Authors: Webb S R , Molnar-Kimber K , Bruce J , Sprent J , Wilson D B
Published: June 2004

A high proportion of T cell clones derived from bulk cultures selected to M1s a,d determinants were found to have joint specificity for allo-H-2 determinants, and vice versa. Significantly, the patterns of H-2 alloreactivity shown by clones selected to M1sa,b determinants appeared to be random. The possible implications of these findings are discussed.
Interstitial mononuclear cell populations in renal graft rejection. Identification by monoclonal antibodies in tissue sections
Authors: Platt JL , LeBien TW , Michael AF
Published: June 2004

The interstitial mononuclear cell populations of 22 renal grafts with interstitial rejection (IR), 6 grafts with interstitial nephritis without rejection (IN), and 5 kidneys without infiltration (3 donor kidneys, 2 grafts) were identified and quantitated by monoclonal antibodies recognizing T cells (TA-1, OKT3), helper inducer cells (OKT4), cytotoxic/suppressor cells (OKT8), B cells (BA-1), and monocytes and null cells (OKM1). Double-layer fluorochrome enhancement using F(ab')(2) reagents and nuclear counter staining with ethidium bromide enabled quantitation of the number of positive mononuclear cells, interstitial cells, and total cells on each of 30-55 microscopic fields per tissue section. T cells were the most abundant infiltrating cell in tissues with IR (35 +/- 9.8 percent), significantly higher than that seen in IN (21 +/- 16 percent) or in kidneys without infiltration (5.0 +/- 3.9 percent). The percentage of T cells identified by TA-1 or OKT3 was approximately equivalent to the summation of OKT4 plus OKT8. Although no differences were observed in the percentage of OKT4 cells, the percentage of OKT8 was significantly higher in IR (26 +/- 7.7 percent, P {less than} 10(-4)) than in IN (9.3 +/- 6.2 percent) or in kidneys with normal interstitium (3.0 +/- 2.4 percent). The ratio of OKT8/OKT4-positive T cells in 22 graft tissues with IR (3.2 +/- 1.4) was greater (P {less than} 0.0007) than 6 graft tissues with IN without rejection (0.82 +/- 0.39) and the 5 kidney tissues without interstitial infiltration (0.75 +/- 0.25). There was no significant difference between the groups in the relatively low percentage of interstitial cells identified as B cells reacting with BA-1 or containing S(IgD,M). The percentage of interstitial cells recognized by OKM1 was similar in rejection and interstitial nephritis, with both being greater than controls (P {less than} 0.02). The relative numbers of blood mononuclear cells identified by the monoclonal antibodies was generally not predictive of the proportions present in kidney tissue, although OKT4-positive blood cells were less numerous and OKMI+ blood cells were more numerous than in controls (P {less than} 0.002).

Quantitative analysis of identifiable interstitial cells in graft rejection reveals that most infiltrating cells are T cells, the greater proportion of which are recognized by OKT8. OKT8-positive cells may play an important role in mediating renal graft rejection.
Murine serum glycoprotein gp70 behaves as an acute phase reactant.
Authors: Hara I , Izui S , Dixon F J
Published: June 2004

A single intraperitoneal injection of bacterial lipopolysaccharide (LPS) or its lipid A component induced high levels of glycoprotein, gp70, in sera of several strains of mice within 24 h. This serum gp70 response induced by LPS was independent of the activation of B cells and the presence of T cells. However, serological and immunohistochemical studies demonstrated the production of gp70 by hepatic parenchymal cells and its subsequent release into the circulating blood. The expression of gp70 in the serum was enhanced not only by LPS but also other inducers of acute phase reactants (APR) such as turpentine oil or polyriboinosinic-polyribocytidylic acid. Further, the serum gp70 response was kinetically identical to those of APR. These results strongly suggest that (a) the liver may be the major source for serum gp70, (b) serum gp70 behaves like an APR, (c) its expression may be controlled by a mechanism similar to that for other APR, and (d) this glycoprotein apparently behaves as a normal host constituent and not a product of a viral genome.
Serial depletion and regeneration of the murine hematopoietic system. Implications for hematopoietic organization and the study of cellular aging
Authors: Ross EAM , Anderson N , Micklem HS
Published: June 2004

The mouse hematopoietic system was subjected to repeated depletion and regeneration either by serial transfer of bone marrow cells through lethally irradiated recipients or by repeated treatment with the cycle-active drug hydroxyurea (HU).

The capacity of surviving stem cells to proliferate and self-renew was assayed at intervals by two methods: (a) the spleen colony method; and (b) competitive repopulation of irradiated recipients using chromosome markers, with normal bone marrow cells as an internal control.

The progressive decline in stem cell function that occurred during serial transfer of bone marrow and that had already begun after a single transfer was not seen during HU treatment; up to 25 pairs of HU injections given over more than 1 yr had no discernible effect on the number of stem cells present 3 wk after the final injection or on their capacity to self-renew.

Within 2 d after exposure to HU, the average self-renewal capacity of surviving stem cells was enhanced. This implies that the drug selectively eliminates poorly self-renewing stem cells and hence that these enter cycle more readily than stem cells with a high self-replicative potential. However, the fact of being in cycle at the time of injection did not of itself affect self-renewal.

The results show that serial transfer of bone marrow is not a valid method for studying clonal aging phenomena because it does not fulfill the assumptions on which such studies are based. No evidence was obtained for any intrinsic limitation in the capacity of bone marrow populations for repeated regeneration after HU-induced depletion. However, this does not necessarily imply that individual hematopoietic clones are capable of indefinite expansion because hematopoiesis may (as suggested by the relative resistance of highly self-replicative stem cells to mitogenic signals) proceed on the basis of clonal succession.
Ocular disease pattern induced by herpes simplex virus is genetically determined by a specific region of viral DNA.
Authors: Centifanto-Fitzgerald Y M , Yamaguchi T , Kaufman H E , Tognon M , Roizman B
Published: June 2004

The pattern of ocular disease produced in the rabbit eye by HSV-1 (F) and HSV-1(MP) strains and recombinants F(MP)A, F(MP)B, F(MP)C, F(MP)D, F(MP)E, and F(MP)F was studied. The characteristics of ocular herpetic disease such as morphology of dendritic ulcers, severity of epithelial disease and incidence and duration of stromal disease produced in the rabbit eye are genetically determined by the virus strain. Our studies show that transfer of a defined part of the genome of the stromal disease-producing virus, HSV-1(MP), to the genome of an epithelial disease-producing virus, HSV-1(F), yielded recombinants with one or more of the disease characteristics of the donor strain. Specifically, recombinant F(MP)D produced lesions characteristic of the donor HSV-1(MP) strain; recombinants F(MP)C and F(MP)E produced stromal disease approaching the severity of the disease produced by the donor HSV-1(MP) strain, and only recombinants F(MP)A and F(MP)B retained the typically elongate lesions of the recipient HSV-1(F), whereas the recombinant strain F(MP)F produced no disease. The viral functions pertaining to the ocular disease pattern map between 0.70 and 0.83 map units in HSV-1 DNA within the BglII F DNA fragment. The pattern of stromal disease is independent of the production of glycoprotein C and fusion of HEp-2-infected cells. The functions relating to these aspects of ocular disease segregate but are closely linked.
Genetic mapping of ecotropic murine leukemia virus-inducing loci in six inbred strains.
Authors: Kozak C A , Rowe W P
Published: June 2004

Mendelian segregation analysis was used to map chromosomal genes for the induction of endogenous N- and B-tropic ecotropic retroviruses (V loci) in high and low leukemic mouse strains. Patterns of virus expression were determined for mice of various inbred strains, congenic lines carrying single V loci, and the linkage testing stocks used in mapping studies. Segregation analysis resulted in the genetic mapping of V loci from six inbred strains to five mouse chromosomes. The V locus of A/J was mapped to chromosome 5 and shown to be allelic with that of BALB/cJ and C3H/HeJ (Cv); this suggests that Cv-represents a stable ancestral V locus present in Bagg albino stocks before the separation of inbred lines. The single, poorly inducible V locus of C57BL/10J and one of the four high virus loci of C58/Lw were mapped to the same region of chromosome 8 and may represent an allelic pair with different patterns of expression. An N-tropic V locus of the SEA/GnJ mouse was mapped to chromosome 9, and one of the three V loci of C3H/FgLw was mapped to chromosome 7. The endogenous B-tropic virus of B10.BR/SgLi was mapped to chromosome 11. These studies provide further evidence that endogenous ecotropic V loci are present at different chromosomal sites in unrelated mouse strains and emphasize the role of germ line reinfections in the generation of this diversity.
Ubiquitous nonimmunoglobulin p-azobenzenearsonate-binding molecules from lymphoid cells.
Authors: Clark A F , Capra J D
Published: June 2004

A ubiquitous nonimmunoglobulin molecule that binds p-azobenzenearsonate (ABA) has been detected in the cytoplasm of several murine cell lines, including T cell hybridomas as well as in normal liver and spleen. Similar to many recently described antigen-specific T cell factors, this ABA-binding protein has a 62,000 mol wt, and, when analyzed by direct binding, the molecule reacts with several different rabbit anti-idiotypic antisera specific to the ABA system. The presence of this antigen-specific, "idiotype positive" molecule in many different cells indicates that it is not an important immunoregulatory molecule.
Generation of T cell colonies from responder strain 2 guinea pigs that recognize the copolymer L-glutamic acid, L-lysine in association with nonresponder strain 13 Ia antigens.
Authors: Clark R B , Shevach E M
Published: June 2004

T cells from nonimmune responder strain 2 guinea pigs were primed in vitro to the copolymer GL in association with allogeneic, nonresponder strain 13 PEC. T cells that recognized GL in association with strain 13 Ia were separated from alloreactive T cells by cloning the population in soft agar following the priming in liquid culture. The existence of T cells of responder origin that recognize antigen in association with nonresponder macrophages is most consistent with clonal deletion models of Ir gene function.
J chain is encoded by a single gene unlinked to other immunoglobulin structural genes.
Authors: Yagi M , D'Eustachio P , Ruddle F H , Koshland M E
Published: June 2004

Immunoglobulin J chain mediates the polymerization of both IgM and IgA immunoglobulins. Its synthesis is closely regulated in B lymphocytes, apparently at the level of RNA transcription. To define the genetic bases of this regulation, we have determined the location and number of J chain genes in the mouse. Analysis of DNA from a group of somatic cell hybrids containing various mouse chromosomes on a constant background of Chinese hamster chromosomes indicated that this gene is located on mouse chromosome 5, unlinked to immunoglobulin heavy and light chain structural genes. Restriction mapping experiments further suggested the existence of a single J chain gene per haploid genome. This result was confirmed by quantitative analyses of band intensities yielded by Southern blots of mouse genomic DNA and J gene-containing plasmid DNA.
Molecular composition of an antigen-specific, Ly-1 T suppressor inducer factor. One molecule binds antigen and is I-J-; another is I-J+, does not bind antigen, and imparts an Igh-variable region-linked restriction.
Authors: Yamauchi K , Chao N , Murphy D B , Gershon R K
Published: June 2004

Immunized Ly-1+2-T cells (Ly-1 cells) make an antigen-specific soluble suppressor product (Lyl-1 TsiF) that will induce Ly-2+ cells to express suppressive activity but only if the Ly-2+ and the Ly-1 producer cell share genetic polymorphisms that are linked to the Igh locus and in particular that part where the Igh-V (or VH) is encoded. Ly-1 TsiF can be separated into entities, one binds antigen and does not express I-J determinants, and the other is I-J+ and does not bind antigen. Neither of these "subfactors" has biological activity, but a 50:50 mixture of them reconstitutes biological activity that expresses the antigen specificity of the antigen-binding molecule. Any of the three heterologous erythrocytes (antigens) studied can be used for immunization to produce the I-J+ nonantigen-binding factor, i.e., the I-J+ moiety makes no contribution to the factor's specificity. It does, however, determine the intact factor's Igh-V linked restriction. Thus, the antigen combining site of the factor is irrelevant to the factor's Igh-V restriction but crucial for its specificity. The I-J+ molecule does not bind antigen nor influence the factor's antigen specificity but expresses the Igh-V polymorphism (or anti-Igh-V polymorphism) that is required for the transmission of an inductive signal to the factor's Ly-2+ acceptor cell.
Features of T cells causing H-2-restricted lethal graft-vs.-host disease across minor histocompatibility barriers.
Authors: Korngold R , Sprent J
Published: June 2004

Evidence is presented that T cells that produce lethal graft-vs.-host disease (GVHD) to minor histocompatibility antigens (minor HA) comprise discrete subgroups of H-2K- and H-2D-restricted T cells; double negative selection of T cells in irradiated H-2 recombinant mice was used to separate these two subgroups. No evidence could be found that I-restricted T cells contributed to GVHD, either as effector cells or helper cells. The (unprimed) precursor cells for GVHD expressed the Thy-1+, Lyt-1+/-2, Ia- phenotype. Studies in which H-2-semiallogeneic bone marrow chimeras were used as hosts for negative selection suggested that presentation of minor HA to T cells during the induction phase is controlled by marrow-derived cells; indirect evidence was obtained that these latter cells can "process" minor HA presented on H-2 different cells and thereby render the antigens immunogenic. Studies in which minor HA-different, H-2-compatible chimeras were re-irradiated and then injected with donor-vs.-host T cells suggested that the effector phase of lethal GVHD involves contact of antigen on non-marrow-derived cells.
Lack of mature B cells in nude mice with X-linked immune deficiency.
Authors: Wortis H H , Burkly L , Hughes D , Roschelle S , Waneck G
Published: June 2004

Mice were bred that simultaneously expressed the mutations nude and x-linked immune deficiency (xid). These doubly deficient animals had less than 10% of normal serum immunoglobulin levels. Their spleen cells did not respond to thymus-independent antigens in vitro nor did they respond to lipopolysaccharide. There was a virtual absence of cells with surface mu, kappa, or lambda 1, as detected by fluorescence. Sections of lymphoid organs revealed an absence of primary B cell follicles. Taken together, these results indicate a lack of mature B cells in nude xid mice. The possibility is considered that mature B cells belong to two subpopulations representing two lineages, one controlled by alleles at the xid locus and the other by alleles at the nude locus.