bluuebunny/crossref_metadata_2025 huggingface dataset:
Early development of the T cell repertoire. In vivo treatment of neonatal mice with anti-Ia antibodies interferes with differentiation of I-restricted T cells but not K/D-restricted T cells.
Authors: Kruisbeek A M , Fultz M J , Sharrow S O , Singer A , Mond J J
Published: June 2004

Monoclonal antibodies to I-Ak were injected into neonatal H-2k mice for a period of 3 wk. The spleens of such mice are devoid of Ia-positive cells. Allo- and trinitrophenyl (TNP)-self-specific cytotoxic T lymphocyte (CTL) responses in such anti-I-A-treated mice were almost completely abrogated at the end of the 2-3 wk in vivo treatment period. Development of suppressor cells, carry-over of blocking antibodies, lack of responder accessory cells, or defective CTL function were not responsible for the observed defect. As concanavalin A supernatant could restore the defect, it is more likely that the defect is due to the absence of competent Ia-specific T helper cells. In addition, anti-I-A-treated mice exhibit reduced I-A antigen expression in the thymus and defective Ia-bearing accessory cell function in the spleen. It is postulated that, for development of Ia-specific T cells to occur, precursor T cells need to interact with Ia-encoded products in the thymus, and anti-Ia treatment interferes with this process. Finally, the mechanism of this interference was shown to be due to actual removal or functional inactivation of those I-A-positive elements responsible for the education of I-A-recognizing T cells, since in (H-2b X H-2k)F1 mice, treatment with anti-I-Ak antibodies results in abrogation of CTL responses to TNP in association with both parental haplotypes, while in the thymus of these mice expression of both I-Ak and I-Ab was reduced.
In vitro differentiation of human monocytes. Monocytes cultured on glass are cytotoxic to tumor cells but monocytes cultured on collagen are not.
Authors: Kaplan G
Published: June 2004

Cultivation of human blood monocytes on glass gives rise to cells nonspecifically cytotoxic to tumor cells. If the monocytes are cultured on collagen gels with no contact with glass, no such cytotoxic activity is induced. Killing appeared to be extracellular and probably contact dependent. The glass-induced cytotoxic activity was not related to protein content or cell viability. Rather, it appeared that the monocytes cultured on glass differentiated into cells resembling activated macrophages. On the other hand monocytes cultured on collagen differentiated into cells resembling resident tissue macrophages. These observations are compatible with numerous studies carried out in rodents, showing that activated macrophages, and not resident cells, are cytotoxic to tumor cells.
B cell activation. I. Anti-immunoglobulin-induced receptor cross-linking results in a decrease in the plasma membrane potential of murine B lymphocytes.
Authors: Monroe J G , Cambier J C
Published: June 2004

We report analyses of the effect of anti-Fab antibodies on plasma membrane potential of mouse B lymphocytes. Results indicate that divalent fragments of anti-Fab antibodies mitogenic for B cells stimulate membrane depolarization detectable by cytofluorometric analysis of 3,3'-dipentyloxacarbocyanine iodide-stained cells. Depolarization is detectable within 5 min of exposure to ligand and maximal within 1 h of exposure when greater than or equal to 80% of splenic B cells exhibit decreased membrane potential. The ineffectiveness of monovalent Fab antibody fragments in inducing this event suggests that receptor immunoglobulin cross-linking is essential. Frequencies of cells induced to enter cell cycle, as assessed by acridine orange cell cycle analysis, are equal to those induced to depolarize by lipopolysaccharide plus dextran sulfate or anti-Fab, which suggests a relationship between these events. However, membrane depolarization is itself an insufficient signal to promote subsequent thymidine uptake, as evidenced by the fact that doses of anti-Fab that are suboptimal for thymidine uptake induce maximal depolarization. These results suggest that cross-linking of surface immunoglobulin on B cells may provide an initial signal for activation but is itself insufficient to drive B cell proliferation.
Presence of IgT-C and I-A subregion-encoded determinants on distinct chains of monoclonal antigen-specific augmenting factor derived from a T cell hybridoma.
Authors: Nakajima P B , Ochi A , Owen F L , Tada T
Published: June 2004

Monoclonal antibodies specific for mouse T cell alloantigens, Tindd and Tsud, linked to the Igh-1 locus on chromosome 12, were used to directly define the antigen-binding molecule produced by a cloned hybridoma. The T cell hybridoma, FL10, was established from antigen-binding T cells of A/J mice. FL10 produces an antigen-specific augmenting T cell factor (TaF) that bears a unique I region-controlled determinant (I-A) and has antigen-binding capacity. The Tindd, but not the Tsud, determinant was detected on the surface of FL10. The presence of both Tindd and I-A subregion-controlled determinants on FL10-derived TaF was directly demonstrated by the adsorption of TaF with immunoadsorbents prepared with monoclonal antibodies. The Igh-1-linked T cell alloantigen, Tsud, was not found on TaF. Further experiments indicated that Tindd is present on the antigen-binding polypeptide chain and not on the second chain bearing the I-A determinant. Despite the presence of the Tindd determinant on hybridoma-derived TaF, augmentation induced by TaF was restricted by the H-2 type of the responding mice and not by the Igh-1 allotype.
Analysis of cross-reactive antigen-specific T cell clones. Specific recognition of two major histocompatibility complex (MHC) and two non-MHC antigens by a single clone.
Authors: Ben-Nun A , Lando Z , Dorf M E , Burakoff S J
Published: June 2004

Two T cell clones, one specific for I-Es/d plus myelin basic protein (BP) and another specific for I-Ak plus influenza virus have been demonstrated to cross-react with DBA/2 cells. Genetic and serological analyses have shown that each clone recognizes its respective priming antigen in association with self-major histocompatibility complex (MHC) determinants and each recognizes DBA/2 minor H antigens in association with allo I-Ad MHC antigens. Further analysis of these clones suggests (a) that the allo I-Ad MHC epitopes recognized by these clones are not shared with self-I-A epitopes, (b) that the virus or BP antigens do not cross-react with DBA/2 minor H antigens, (c) that these clones recognize different determinants on the DBA/2 minor H antigens, and (d) that there is a requirement for a specific association between the different MHC antigens and the non-MHC antigens to stimulate these clones. This specific associative recognition argues strongly for the "altered self" hypothesis.
Structural heterogeneity of the C3b/C4b receptor (Cr 1) on human peripheral blood cells.
Authors: Dykman T R , Cole J L , Iida K , Atkinson J P
Published: June 2004

In these studies CR 1 polymorphism previously demonstrated on erythrocytes (E) was also found on CR 1-bearing peripheral blood leukocytes including polymorphonuclear (PMN), eosinophils, monocytes, and B lymphocytes. However several cell-specific differences in CR1 were found: (a) an approximately 5,000-dalton increase in CR 1 on PMN and eosinophils, (b) unequal band intensity among heterozygotes suggests that there is preferential expression of 220,000- or 225,000-dalton receptors on leukocytes compared to E, and (c) "minor" bands, approximately 15,000 daltons larger than the major receptor molecule, were found on E but not on leukocytes. These observations constitute a unique example of heterogeneity of an integral membrane receptor.
Deficiency in suppressor T cell activity in aged animals. Reconstitution of this activity by interleukin 2.
Authors: Thoman M L , Weigle W O
Published: June 2004

Spleen cells derived from aged (30 mo) C57Bl/6 mice are shown to be deficient in the ability to generate suppressor cell activity in vitro. The addition of IL-2 to cultures containing aged cells restores this function to a large extent.
Immunoregulatory T cell circuits in man. Alloantigen-primed inducer T cells activate alloantigen-specific suppressor T cells in the absence of the initial antigenic stimulus.
Authors: Damle N K , Engleman E G
Published: June 2004

Although alloantigen-specific suppressor T cells are generated in MLR, the cellular signals that lead to activation of suppressor T cells as opposed to cytotoxic T cells are unknown. The current study was undertaken to characterize interactions among T cell subsets involved in the generation of suppressor T cells in MLR. Human peripheral blood Leu-2+ (suppressor/cytotoxic) and Leu-3+ (helper/inducer) T cell subsets were activated with allogeneic non-T cells and then examined for their inductive effects on fresh autologous T cells. Fresh Leu-2+ cells proliferated in response to alloantigen-primed Leu-3+ cells and subsequently suppressed the response of fresh autologous Leu-3+ cells to the original, but not third party, allogeneic stimulator non-T cells. Moreover, only Leu-2+ cells that lacked the 9.3 marker, an antigen present on the majority of T cells including precursors of cytotoxic T cells, differentiated into suppressor cells. The alloantigen-specific suppressive effect of Leu-2+,9.3-cells was not mediated by cytolysis of allogeneic stimulator cells, nor could it be explained by alteration of MLR kinetics. Suppression was observed only when activated Leu-2+ cells were added to fresh MLRs within 24 h of initiation of cultures, suggesting that these cells block an early phase of the activation of Leu-3+ cells in MLR. These results indicate that alloantigen-primed inducer T cells can activate alloantigen-specific suppressor T cells in the absence of allogeneic stimulator cells.
Enhancing effect of H-2-linked NZW gene(s) on the autoimmune traits of (NZB X NZW)F1 mice.
Authors: Hirose S , Nagasawa R , Sekikawa I , Hamaoki M , Ishida Y , Sato H , Shirai T
Published: June 2004

To investigate the possible enhancing effect of the H-2z haplotype of the New Zealand White (NZW) strain on the production of autoantibodies and renal disease observed in B/W F1 mice, we developed the ZWD/8 strain, a NZW congenic line carrying the H-2d haplotype, produced (NZB X ZWD/8)F1 (B/WD8 F1) mice, and examined the difference in several immunological abnormalities between the B/W F1 (H-2d/H-2z) and the B/WD8 F1 (H-2d/H-2d) mice. In comparison with B/W F1 mice, the B/WD8 F1 mice showed markedly lower serum levels of the anti-DNA antibodies and the gp70 ICs, and a later onset and a lower incidence of proteinuria with a lower mortality. In contrast, there was no significant difference in the incidences and the amounts of both natural thymocytotoxic autoantibody and anti-erythrocyte autoantibody between these two hybrid strains. Further, the serum levels of IgG and IgM in B/WD8 F1 mice were as high as those in B/W F1 mice. These findings indicate that the gene(s) that is within or closely linked to the H-2 complex of NZW strain specifically acts to intensify the levels of anti-DNA antibodies and gp70 ICs, and to promote the severity of renal disease in B/W F1 mice. This gene may play a role in the class conversion of anti-dsDNA antibodies from IgM to IgG.
Lymphokine enhances oxygen-independent activity against intracellular pathogens.
Authors: Murray H W , Byrne G I , Rothermel C D , Cartelli D M
Published: June 2004

To determine if mechanisms other than the generation of toxic oxygen intermediates are active against intracellular pathogens, oxidatively deficient mouse L cells and monocyte-derived macrophages from patients with chronic granulomatous disease were stimulated with soluble lymphocyte products. Despite no enhancement in oxidative activity, these cells displayed effective microbistatic activity against both T. gondii and C. psittaci. These results suggest a potential role for nonoxidative mechanisms in the mononuclear phagocyte's activity against intracellular pathogens, and indicate that lymphokines can regulate both oxygen-dependent and oxygen-independent antimicrobial responses.
Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology.
Authors: De Fabo E C , Noonan F P
Published: June 2004

UV irradiation of mice causes a systemic immune alteration that can be detected either by suppression of the immunologic rejection of UV-induced tumors, or by suppression of contact hypersensitivity (CHS). Suppression of these two immunologic responses has similar photobiologic characteristics and in both cases is associated with the generation of antigen-specific suppressor T cells. To identify whether a specific photoreceptor for this effect exists, the relative wavelength effectiveness (action spectrum) was determined for the UV-induced suppression of CHS. Narrow bands of UV (half bandwidth 3 nm) were used at 10 wavelengths from 250 to 320 nm to obtain dose-response curves. Irradiation with each of these bands of UV caused dose-dependent immunosuppression of CHS, but with differing effectiveness. Immunosuppression was clearly separable from the generation of gross skin damage and inflammation. Further, immunosuppression by the most effective wavelength (270 nm) was associated with the generation of antigen-specific suppressor cells. The action spectrum derived from the dose-response curves has a maximum between 260 and 270 nm, a shoulder at 280-290 nm, and declines steadily to approximately 3% of maximum at 320 nm. The finding of such a clearly defined wavelength dependence implies the presence of a specific photoreceptor for this effect. Removing the stratum corneum by tape stripping before UV irradiation prevented the suppression of CHS using 254-nm radiation, suggesting the photoreceptor is superficially located in the skin. A number of epidermal compounds with absorption spectra similar to the action spectrum are discussed and evaluated with respect to their potential for being the photoreceptor. Based on (a) the close fit of its absorption spectrum to the action spectrum, (b) its superficial location in the stratum corneum, and (c) its photochemical properties, the hypothesis is advanced that the photoreceptor for systemic UV-induced immunosuppression of contact hypersensitivity may be urocanic acid. As such, it may also play a role in UV-induced carcinogenesis via the production of tumor-specific suppressor cells.
Cell membrane perturbation of resting T cells and thymocytes causes display of activation antigens.
Authors: Mittler R S , Rao P E , Talle M A , Look R , Goldstein G
Published: June 2004

Three human lymphocyte antigens recognized by monoclonal antibodies OKIa1, OKT9, and OKT10 were found to be minimally represented on resting peripheral T cells (all three) and thymocytes (OKIa1 and OKT9). These antigens, which are present on "activated" T cells, were promptly displayed on "resting" T cells or thymocytes following cross-linking of surface-bound monoclonal antibody by horse alpha-mouse IgG. These experiments suggested that membrane perturbations may induce the expression of certain antigens that are normally present in an unexpressed form in resting cells.
Subpopulations of B cells distinguished by cell surface expression of Ia antigens. Correlation of Ia and idiotype during activation by cloned Ia-restricted T cells.
Authors: Bottomly K , Jones B , Kaye J , Jones F
Published: June 2004

We have investigated in vitro the induction of antibody responses to phosphorylcholine (PC) by cloned T helper (Th) cell lines. The cloned Th cells are antigen specific, in this case ovalbumin (OVA), self-Ia recognizing, and induce antibody secretion only if the hapten, PC, is physically linked to the carrier (OVA) molecule. The plaque-forming cell (PFC) response generated in the presence of cloned Th cells is idiotypically diverse with 5-40% of the secreting B cells bearing the TEPC-15 (T15) idiotype. The interaction of the cloned Th cells and unprimed B cells requires recognition of B cell surface Ia glycoproteins for all B cells activated to secrete anti-PC antibody, whether they be T15-bearing or not. More importantly, however, effective interaction between a cloned Th cell and a B cell is determined by the quantity of B cell surface Ia glycoproteins. Our results indicate that quantitative differences in B cell surface Ia antigens are directly related to B cell activation by the cloned Th cell. The high Ia density B cells are most easily activated by cloned Th cells, and these appear to be mainly non-T15-bearing. These data suggest that the failure of cloned Th cells to effectively activate T15-bearing B cells in vitro may be due to the lower relative Ia density of these B cells and therefore to their inability to interact effectively with cloned Ia-recognizing Th cells. These results imply that monoclonal T cells may distinguish between T15-bearing and non-T15-bearing B cells based on their Ia density.
A new gene that controls the type of leukemia induced by Friend murine leukemia virus.
Authors: Silver J E , Fredrickson T N
Published: June 2004

NB tropic Friend murine leukemia virus (F-MuLV) replicates equally well in BALB/c and C57BL mice inoculated as neonates but causes almost exclusively erythroblastosis in BALB/c mice and nonerythroid (lymphoid and myelogenous) leukemias in C57BL mice. The C57BL resistance to erythroblastosis appears to be controlled by a single dominant gene in first and second backcrosses to BALB/c. This resistance to erythroblastosis is distinct from other genes known to affect susceptibility to Friend virus including Fv-1, Fv-2, H-2, Rfv-3, Fv-4, and Rmcf. We suggest the name Fhe for the new gene controlling susceptibility to Friend helper virus erythroblastosis.
Epstein-Barr virus transformation of human pre-B cells.
Authors: Hansson M , Falk K , Ernberg I
Published: June 2004

In vitro infection of human B lymphocytes with Epstein-Barr virus (EBV) results in establishment of B lymphoblastoid cell lines that reflect normal B cell phenotypes. In this study we have investigated whether immature B cells from fetal bone marrow and liver can serve as targets for EBV. The fetal bone marrow cells were readily transformed by EBV. Among the resulting cell lines, five were surface Ig (sIg)-negative. Three B cell-associated antigens defined by monoclonal antibodies were expressed to the same extent on the fetal cell lines, whether they belonged to the sIg- or sIg+ group. The various differentiation stages that these cell lines may represent are discussed.
Amyloid fibril in hereditary cerebral hemorrhage with amyloidosis (HCHWA) is related to the gastroentero-pancreatic neuroendocrine protein, gamma trace.
Authors: Cohen D H , Feiner H , Jensson O , Frangione B
Published: June 2004

Amyloid fibrils were isolated from the leptomeningeal blood vessels obtained at autopsy from three Icelandic patients dying of Hereditary Cerebral Hemorrhage with Amyloidosis (HCHWA) and verified by Congo red staining and electron microscopy. Gel filtration on Sephadex and Ultrogel columns yielded predominantly one component (molecular weight 11,500 daltons) and also another minor component (molecular weight 15,800 daltons). Automated amino terminal sequencing showed these proteins to be similar (36 residues) to a recently described human protein, gamma trace, beginning at its eleventh amino terminal residue. The amyloid deposits in all three patients stained with rabbit anti-gamma trace antiserum. Although the function of gamma trace is not known, it appears to have structural homology with several hormones and has been localized to the brain, pancreas and pituitary. The amyloid fibril subunits seem to have polymerized after cleavage of the amino terminal decapeptide from gamma trace-related proteins. Therefore, HCHWA appears to be the first genetically determined disease related to the gastroenteropancreatic neuroendocrine system.
Activation of antigen-specific suppressor T cells by B cells from mice immunized with type III pneumococcal polysaccharide.
Authors: Taylor C E , Stashak P W , Caldes G , Prescott B , Chused T E , Brooks A , Baker P J
Published: June 2004

The transfer of B lymphocytes from mice immunized with type III pneumococcal polysaccharide (SSS-III) results in antigen-specific suppression of the antibody response of recipients immunized with SSS-III. Such suppression shares many features associated with low-dose paralysis, a phenomenon mediated by suppressor T cells; it reaches maximal levels 3 d after the transfer of viable or irradiated immune B cells and can be eliminated by the depletion of SSS-III-binding cells from spleen cell suspensions before transfer. In a two-step cell transfer experiment, purified T lymphocytes, isolated from recipients previously given immune B cells, caused suppression upon transfer to other mice immunized with SSS-III. Also, B-cell-induced suppression could be abrogated in a competitive manner by the infusion of amplifier T lymphocytes, as was previously demonstrated in the case of low-dose paralysis. These findings suggest that B cell surface components, presumably the idiotypic determinants of cell-associated antibody specific for SSS-III, are instrumental in activating suppressor T cells involved in regulating the magnitude of the antibody response to SSS-III.
Evidence for two distinct classes of murine B cell growth factors with activities in different functional assays.
Authors: Swain S L , Howard M , Kappler J , Marrack P , Watson J , Booth R , Wetzel G D , Dutton R W
Published: June 2004

Several previously described B cell growth factor (BCGF) activities from a number of mouse monoclonal T cell sources were compared in different functional assays. The results indicate that there are two distinct classes of BCGF defined by functional activity and source. BCGF I, whose prototype is (EL4)BCGF, synergized with anti-Ig in the proliferation of normal splenic B cells but had no activity when dextran sulfate (DXS), rather than anti-Ig, was used to costimulate the same source of B cells. BCGF I also failed to directly stimulate BCL1 tumor B cells. In contrast, BCGF II, whose prototype is (DL)BCGF, showed a reciprocal pattern of activity. BCGF II failed to synergize with anti-Ig-costimulated normal B cells to give good proliferative responses. Sources of BCGF II also directly stimulated (no anti-Ig or DXS added) B cells of the BCL1 tumor-carrying mice. These results suggest that the two BCGF may have activity on two subsets of B cells that respond differentially to induction with the two polyclonal B cell activators, anti-Ig and DXS. The possibilities that these different patterns of response occur in separate lineages of B cells and/or in B cells in different states of differentiation is discussed.
Allogeneic induction of the human T cell-instructed monocyte procoagulant response is rapid and is elicited by HLA-DR.
Authors: Helin H , Edgington T S
Published: June 2004

The recognition of alloantigens by human lymphoid cells initiates a collaborative cellular pathway that rather rapidly induces in adherent cells (monocytes) the synthesis and expression of cell surface tissue factor, the initiating cofactor of the extrinsic coagulation pathway. This response was vigorous, generating tissue factor to a level nearly comparable to the response to endotoxin. However, it was temporally discordant with characterized lymphoid procoagulant responses to endotoxin, virus, and immune complexes in that it reached a maxima at 48 h, well after these other responses but clearly much faster than the well recognized proliferative responses to allogeneic stimulation. Using the Daudi lymphoblastoid B cell line, the allogeneic response could be fully elicited in a dose-dependent fashion within 18 h. The induction of monocyte tissue factor required collaboration with T lymphocytes, in accord with previously described T cell-instructed monocyte responses. HLA-DR was implicated as the allogeneic signal by the ability of two monoclonal antibodies to completely block, in a dose-dependent fashion, the induction of this pathway. Notably, the allogeneic procoagulant response was quantitatively discordant with respect to the allogeneic proliferative response, suggesting differences in specificity. This relatively rapid response may be applicable to typing of determinants in the major histocompatibility complex that are not equivalently identified by alternative analyses, and may be significant in tissue transplantation. The cellular pathway, linking allogeneic recognition with induction of a monocyte response that initiates the coagulation pathway, represents a further example of the linkage between these biologic systems, and is consistent with a pathogenetic role in allograft rejection by the promotion of vascular thrombosis and interstitial fibrin accumulation.
Lysis of inducer T cell clones by activated macrophages and macrophage-like cell lines.
Authors: Rao A , Faas S J , Miller L J , Riback P S , Cantor H
Published: June 2004

We describe a sequence of reciprocal interactions between cloned inducer T cells and antigen-presenting cells (APC) that results in selective depletion of the antigen-reactive inducer cells. We show that corecognition of antigen and I-A by hapten-reactive inducer T cell clones results in (a) release of macrophage-activating factor (MAF) and other lymphokines, (b) expression of lytic activity by a subset of MAF-sensitized APC after triggering, and (3) lysis (mediated by the activated and triggered macrophage) of the inducer T cell clone and other cells in the vicinity. We suggest that this sequence of steps may limit the extent of macrophage-mediated tissue destruction by depleting the specific inducer T cell clones that initiate the response.
Lymphokine-activated killer cell phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells.
Authors: Grimm E A , Robb R J , Roth J A , Neckers L M , Lachman L B , Wilson D J , Rosenberg S A
Published: June 2004

Purified interleukin 2 (IL-2) was found to be sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer (LAK) cells. The LAK activation factor was directly and consistently associated with IL-2 activity using classic protein purification techniques, adsorption to IL-2-dependent cell lines, and inhibition with anti-Tac antibody. As yet, no other cytokines have been found that perform the same role.
Peptide variability exists within alpha and beta subunits of the T cell receptor for antigen.
Authors: Acuto O , Meuer S C , Hodgdon J C , Schlossman S F , Reinherz E L
Published: June 2004

The T cell receptor for antigen (Ti) has recently been identified as a 90-kdalton T3-associated clonotypic structure composed of one 49-51-kdalton alpha and one 43-kdalton beta subunit, which are disulfide linked. Here, Ti molecules from two alloreactive CTL clones derived from the same donor but of differing specificities (CT8III and CT4II) are directly compared following isolation with anticlonotypic monoclonal antibodies. Isoelectric focusing shows that the alpha subunits (pI 4.4-4.7) are more acidic than the beta subunits (pI 6.0-6.2) but that each glycoprotein species is distinctive. More importantly, two-dimensional peptide maps of 125I-labeled surface receptors indicate that the beta chains of Ti1 and Ti2 appear unique and share only two peptides in common. In contrast, peptide maps of Ti1 and Ti2 alpha chains are more related although not identical. These results suggest that the human T cell receptor is composed of constant as well as variable regions and that at least one of the latter is located within the beta subunit.
Susceptibility to Friend helper virus leukemias in CXB recombinant inbred mice.
Authors: Silver J E , Fredrickson T N
Published: June 2004

The seven CXB recombinant inbred strains were tested for susceptibility to Friend helper virus (F-MuLV) hematopoietic neoplasms. BALB/c and CXB-H mice develop erythroblastosis after neonatal inoculation with F-MuLV, while C57BL/6 and the six other RI strains develop lymphoma and myelogenous leukemia. This strain distribution pattern is different from that for H-2, Gpd-1 (linked to Fv-1), Fv-2, Rfv-3, and Cv (linked to Rmcf) but the same as that for Bv, the endogenous ecotropic virus of C57BL/6. However, analysis of crosses segregating Bv show that resistance to F-MuLV erythroblastosis is not linked to Bv. Disease-free survival is shortest for BALB/c mice, intermediate for CXB-H and CXB-J, and longest for C57BL/6 and the other RI strains. We conclude: (a) the major C57BL/6 gene for resistance to F-MuLV erythroblastosis is different from previously identified Friend virus restriction loci; (b) latency for F-MuLV leukemias is controlled by more than one gene; and (c) latency and susceptibility to F-MuLV erythroblastosis are not inherited concordantly in the CXB-RI strains.
Covalent attachment of soluble proteins by nonenzymatically glycosylated collagen. Role in the in situ formation of immune complexes.
Authors: Brownlee M , Pongor S , Cerami A
Published: June 2004

The chronic tissue damage associated with long-term diabetes mellitus may arise in part from in situ immune complex formation by accumulated immunoglobulins and/or antigens bound to long-lived structural proteins that have undergone excessive nonenzymatic glycosylation. In this report, we have tested this hypothesis using nonenzymatically glycosylated collagen. Binding of both albumin and IgG averaged four times the amount bound to unmodified collagen. Both albumin and IgG (anti-BSA) bound to nonenzymatically glycosylated collagen retained their ability to form immune complexes in situ with free antibody and antigen.
Cross-reactivity of self-HLA-restricted Epstein-Barr virus-specific cytotoxic T lymphocytes for allo-HLA determinants.
Authors: Gaston J S , Rickinson A B , Epstein M A
Published: June 2004

Epstein-Barr (EB) virus-specific cytotoxic T cells, prepared from virus-immune donors by reactivation in vitro and maintained thereafter as IL-2-dependent T cell lines, have been tested against large panels of EB virus-transformed lymphoblastoid cell lines of known HLA type. Whilst the pattern of lysis of the majority of targets was always consistent with HLA-A and HLA-B antigen restriction of effector function, in several cases it was noticed that certain HLA-mismatched targets were also reproducibly lysed. When this "anomalous" lysis was investigated in detail, it was found to be directed against allodeterminants on class I HLA antigens; thus, mitogen-stimulated as well as EB virus-transformed lymphoblasts from the relevant target cell donors were sensitive to the killing, and in each case the lysis could be specifically blocked by monoclonal antibodies to class I HLA antigens. In one example the target for this alloreactive lysis could be identified as a single serologically defined antigen, HLA-Bw57, while in another example lysis was directed against a "public" epitope common to HLA-Bw35, -Bw62, and a subset of -B12 antigens. Both cold target inhibition experiments and limiting dilution analysis strongly suggested that this alloreactive lysis was being mediated by the same effector T cells that recognize EB viral antigens in the context of self-HLA. This is the first demonstration in man that alloreactive responses can be derived from within the antigen-specific, self MHC-restricted T cell repertoire.
Tolerance for self IG at the level of the Ly1+ T cell.
Authors: Bikoff E K
Published: June 2004

Experiments presented in this report demonstrate that specificity of the Ly1+ T cell proliferative response to NP-modified Ig is controlled by Igh-C-linked genes. In addition, we describe the mechanism whereby Igh-C-encoded molecules influence Ly1+ T cell activity. We show that Igh-C-linked control of T cell responses to NP-modified Ig is a secondary consequence of naturally acquired tolerance for self Ig. Unresponsiveness to self Ig is not due to a defect expressed functionally at the level of the antigen-presenting cell, nor is it associated with active suppression. These results suggest that tolerance for self Ig at the level of the Ly1+ T cell is due to functional deletion of Ly1+ T cell clones specific for self Ig. The possibility is considered that regulatory effects mediated by passively administered antibodies may in part be due to induction of Ly1+ T cell tolerance for self Ig.
Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes.
Authors: Wright S D , Silverstein S C
Published: June 2004

We have measured the release of H2O2 from granulocytes, monocytes, and macrophages during spreading on ligand-coated culture surfaces. While IgG-coated surfaces stimulate vigorous release of H2O2, neither C3b- nor C3bi-coated surfaces promoted appreciable release of H2O2 despite full ligation of C3b and C3bi receptors. We also measured release of H2O2 from cultured monocytes spreading on surfaces coated with both fibronectin and C3. Under such circumstances, the C3 receptors elicit a strong phagocytic response, but no H2O2 release was recorded. We conclude that the C3b and C3bi receptors of monocytes and granulocytes do not signal the generation of toxic oxygen intermediates from these cells.
Immune interferon and leukocyte-conditioned medium induce normal and leukemic myeloid cells to differentiate along the monocytic pathway.
Authors: Perussia B , Dayton E T , Fanning V , Thiagarajan P , Hoxie J , Trinchieri G
Published: June 2004

Conditioned medium from phytohemagglutinin-stimulated human leukocytes contains a factor that can induce promyelocytic cell lines and certain acute myelogenous leukemia cells to differentiate along the monocytic pathway. In this report, we show that immature myeloid cells from normal bone marrow or the peripheral blood of patients with chronic myelogenous leukemia can be induced to differentiate to monocyte-like cells by immune gamma interferon (IFN gamma). We have identified IFN gamma as the predominant differentiation factor contained in the conditioned medium. Purified or recombinant IFN gamma, but not various preparations of IFN alpha or beta, can induce monocytic differentiation in myeloid cells. In cultures containing conditioned medium, the cells fail to continue myeloid maturation, and are induced to express monocyte markers and functions, such as monocyte-specific surface antigens, HLA-DR antigens, Fc receptors for monomeric immunoglobulins, nonspecific esterase, and the ability to mediate antibody-dependent, cell-mediated cytotoxicity. Even myeloid cells as mature as metamyelocytes or band cells can be induced by IFN gamma to undergo monocyte differentiation, but monocyte-specific or HLA-DR antigens are not induced in mature neutrophils. These findings reveal a previously unknown, specific function of human IFN gamma and offer new insights to the regulation of monocyte recruitment and differentiation during a virus infection or immune response.
Fine idiotype analysis of B cell precursors in the T-dependent and T-independent responses to alpha 1-3 dextran in BALB/c mice.
Authors: Stohrer R , Kearney J F
Published: June 2004

In this study BALB/c B cell precursors responsive to the T-independent (TI) type 2 (TI-2) antigen, dextran B1355S (DEX), and the T-dependent (TD) derivative, dextran-Limulus hemocyanin (DEX-Hy) were examined for isotype and idiotope expression using the splenic focus assay. The predominant isotype detected in the TI assay was IgM, while IgA was the predominant isotype expressed in the TD assay. There was also a fourfold increase in the number of foci secreting more than one isotype in the TD assay vs. the TI assay without an overall change in anti-DEX precursor frequency, suggesting that carrier-primed T cells enhance the expression of non-IgM isotypes possibly by increasing the frequency of isotype switching by individual B cell precursors. A panel of distinct monoclonal antiidiotype antibodies (MAIDs) was then used to examine idiotope expression by antibodies secreted in splenic foci responding to DEX and DEX-Hy. This analysis revealed considerable diversity in the idiotope profiles expressed by all isotypes tested. There appeared to be no differences in idiotope diversity among the various isotypes. A similar diversity of idiotope profiles was obtained from both TI and TD splenic foci, indicating that a comparable degree of diversity was associated with the antibodies generated by TI and TD precursors. Idiotype analysis of IgM-IgA-secreting foci with a panel of monoclonal antiidiotope antibodies revealed slight idiotypic differences between the two isotypes secreted in the same focus in about half the cases. These results suggest that somatic variation occurs during the antigen-driven maturation of B cell precursors, within the 15-d time frame of the splenic focus assay, and may be associated with isotype switching.
Multiple VH gene segments encode murine antistreptococcal antibodies.
Authors: Perlmutter R M , Klotz J L , Bond M W , Nahm M , Davie J M , Hood L
Published: June 2004

Most mouse strains are able to mount a diverse antibody response against group A streptococcal carbohydrate (GAC). We have previously reported that murine anti-GAC antibodies are for the most part restricted to IgM and IgG3 subclasses. In addition, despite extensive heterogeneity in their isoelectric focusing patterns, greater than 50% of A/J anti-GAC antibodies share a common light chain defined by spectrotypic and idiotypic (VK1GAC) criteria. We have used protein and DNA sequencing strategies to examine the genetic basis of diversity in murine anti-GAC antibodies. In particular, we report that, (a) multiple, closely homologous VH gene segments contribute to the generation of anti-GAC antibodies, (b) a common framework sequence, related to the VK27 subgroup, probably defines VK1GAC, and (c) the A/J anti-GAC VH regions and BALB/c anti-inulin VH sequences are 95% homologous at the protein level and are likely encoded by overlapping VH gene families. Lastly, we discuss the genetic mechanisms that might permit the evolution of multiple, closely homologous germline VH gene segments in the context of highly divergent flanking region sequences.
Direct transfer of antigen-specific cytolytic activity to noncytolytic cells upon fusion with liposomes derived from cytolytic T cell clones.
Authors: Harris D T , MacDonald H R , Cerottini J C
Published: June 2004

Murine cytolytic T lymphocytes (CTL) clones were solubilized in Nonidet P-40 detergent, and the matrix and membrane proteins separated from the nuclear constituents. These proteins, in combination with exogenous lipids and Sendai virus envelope proteins, were used to construct liposomes that were then fused with noncytolytic cloned T cell recipients. The resultant fusion products were found to be highly cytolytic and appeared to express the same specificity as the original donor clone. Further analysis showed that the liposomal transfer process was extremely efficient. Moreover, in addition to noncytolytic T cell clones, three transformed T cell lines and one B cell line were found to express specific cytolytic activity after fusion with appropriate liposomes. Inhibition experiments using monoclonal antibodies against target cell antigens, as well as analysis of the lytic reactivity pattern of the fusion products, confirmed the high degree of specificity conferred to the recipient cells. This study thus indicates that the two characteristics typically associated with CTL, namely antigen-specific recognition and cytolytic activity, can be solubilized from CTL and transferred to recipient cells that do not express these characteristics.
Immunocytochemical identification and quantitation of the mononuclear cells in the cerebrospinal fluid, meninges, and brain during acute viral meningoencephalitis.
Authors: Moench T R , Griffin D E
Published: June 2004

The mononuclear cells of the central nervous system (CNS) inflammatory response were characterized in cerebrospinal fluid (CSF), meningeal exudate, and brain parenchyma of mice 3-14 d after infection with Sindbis virus. The inflammatory infiltrate in CSF peaked and resolved before that of the parenchyma or meningeal exudate. Immunoperoxidase staining with monoclonal antibodies identified CSF inflammatory cells to be almost exclusively T cells, while inflammatory cells in the brain parenchymal perivascular cuffs and the meninges were a mixture of T cells, B cells, and macrophages. The percentage of B cells and macrophages increased at the later time points. Approximately 20% of CSF and 50% of the cells present early in the perivascular cuffs were not identified, suggesting that another subset of inflammatory cells may be present. We concluded that significant differences exist in the time course and cellular composition of the inflammatory responses in different compartments of the CNS during an acute viral infection.
Cytotoxic T lymphocyte recognition of the influenza hemagglutinin gene product expressed by DNA-mediated gene transfer.
Authors: Braciale T J , Braciale V L , Henkel T J , Sambrook J , Gething M J
Published: June 2004

We have used the technique of DNA-mediated gene transfer to examine cytotoxic T lymphocyte (CTL) recognition of the product of the cloned A/JAPAN/305/57 hemagglutinin (HA) gene in murine (L929) cells. Using both heterogeneous and homogeneous (clonal) populations of type A influenza-specific CTL, we have demonstrated that the HA molecule can serve as a target antigen for both the subtype-specific and the cross-reactive subpopulations of influenza-specific CTL. Our results also raise the possibility that other virus-specified polypeptides may serve as target molecules for cross-reactive CTL.
Purification and partial characterization of the opacity-associated proteins of Neisseria gonorrhoeae.
Authors: Blake M S , Gotschlich E C
Published: June 2004

Gonococci, grown on agar, frequently give rise to opaque colonies. This opacity phenotype is associated with the presence of one or more outer membrane proteins of approximately 28,000 mol weight. These proteins are included within a class of proteins named proteins II. A method is described to isolate and purify the opacity-associated proteins from Neisseria gonorrhoeae. This method uses high concentrations of calcium and a zwitterionic detergent at pH 4.0. Under these conditions proteins II are readily solubilized from the outer membrane. Further purification is achieved by ion exchange and molecular sieve chromatography in the presence of the zwitterionic detergent. The opacity-associated proteins are very basic with isoelectric points varying between 9.0 to 10.0. Further evidence for their basic nature is their behavior on ion exchange chromatography and their amino acid composition.
Antibody producing human-human hybridomas. II. Derivation and characterization of an antibody specific for human leukemia cells.
Authors: Olsson L , Andreasen R B , Ost A , Christensen B , Biberfeld P
Published: June 2004

Human-human hybridoma technology was used to immortalize human B lymphocytes from patients with acute myeloid leukemia (AML) to study the antigenic repertoire of the humoral immune response against the patients' own leukemia cells and against leukemic cells from other patients. Nine fusions were done with lymphocytes from seven AML patients, and all with the human RH-L4 B lymphoma line as malignant fusion partner. A total of 305 Ig-producing hybrids were obtained. 26 reacted with cell surface components on AML cells, but 21 were found not to be specific for leukemia cells, when screened for reactivity against a panel of normal and malignant cells of both human and murine origin. Five hybridomas secreted Ig with high specificity for human leukemia cells, but only one hybridoma culture, aml-18, was stable in respect to Ig-production and growth upon repeated clonings and expansion in liquid cultures. A method was developed to grow human hybridomas as ascites tumors in nude mice, but the ascites fluid did not contain increased amount of antibody. The reactivity of the aml-18 antibody (gamma, kappa) was analyzed against samples of mononuclear cells from peripheral blood of 63 patients with leukemia and with cytologically verified leukemia cells in the blood. 22 of 54 AML samples reacted with aml-18. The reactivity pattern was not correlated to any categories of the French-American-British (FAB) classification; two of four ALL were positive. Moreover, a pronounced intratumoral antigenic heterogeneity in regard to aml-18 reactivity was seen and indicates a high degree of diversity in the immunological phenotype within individual AML cell populations. The study demonstrates that some patients with AML generate an immune response against their autologous malignant cells, and that the antigenic determinant in the case of aml-18 is also expressed specifically on leukemic cells from other patients.
The thyroid "microsomal" antibody revisited. Its paradoxical binding in vivo to the apical surface of the follicular epithelium.
Authors: Khoury E L , Bottazzo G F , Roitt I M
Published: June 2004

We have shown that thyroid monolayers derived from the glands of patients with autoimmune thyroid disease have immunoglobulin (Ig) bound to their surface. This appears to have been deposited in vivo rather than during preparation of the monolayers, a view supported by our finding of such deposits on the apical margin of follicular cells in sections cut from these glands and stained with conjugated anti-immunoglobulin. It is likely that these deposits represent specific binding of so-called "microsomal" autoantibodies to the surface of the thyroid cells in vivo since staining of partially disrupted follicles ("half-melons") with Hashimoto serum containing microsomal autoantibodies in the indirect immunofluorescence (IFL) test, localized the antigen on the apical surface of the cells lining the follicular cavity. Thus, paradoxically, although the antigen is relatively inaccessible, autoantibodies do reach and combine with the thyroid surface in vivo and may therefore play a role in pathogenesis.
Differential effects of hydrogen peroxide on indices of endothelial cell function.
Authors: Ager A , Gordon J L
Published: June 2004

The responses of pig aortic endothelial cells to sublethal doses of potentially toxic stimuli were investigated by monitoring K+ efflux, prostaglandin production, and the release of cytoplasmic purines. Xanthine plus xanthine oxidase reversibly stimulated these three parameters of endothelial cell function at doses that were not cytotoxic, as measured by chromium release, adenine uptake, and vital dye exclusion. The effects of xanthine plus xanthine oxidase were inhibited by catalase but not by superoxide dismutase, suggesting that H2O2 was responsible. Reagent H2O2 also reversibly stimulated K+ efflux, prostaglandin production, and the release of purines. The threshold concentration of H2O2 for these effects was approximately 10 microM, which was at least 30-fold lower than that which caused cytotoxicity. In addition to the direct effect of H2O2 in stimulating prostaglandin production (PGI2 and PGE2), prior exposure of endothelial cells to lower doses of H2O2 (less than 0.1 microM) at high oxygen tension inhibited the subsequent stimulation of prostaglandin production by ATP, A23187, and H2O2 itself. We conclude that H2O2 has substantial effects on endothelial physiology at doses up to 3,000-fold lower than those which induce cytotoxicity.
Enhancement of the immune response to hepatitis B surface antigen. In vivo administration of antiidiotype induces anti-HBs that expresses a similar idiotype.
Authors: Kennedy R C , Dreesman G R
Published: June 2004

BALB/c mice receiving antiidiotype antibodies before the injection of hepatitis B surface antigen (HBsAg) generated an enhanced anti-HBs response. Mice given antiidiotype antibodies in a soluble form induced predominantly IgM anti-HBs, whereas alum-precipitated antiidiotype produced primarily IgG anti-HBs. Injection of antiidiotype antibodies alone induced anti-HBs that inhibited a common interspecies anti-HBs idiotype-antiidiotype reaction and recognized the group-specific determinant of HBsAg. These data support the view that antiidiotype antibodies may modulate the immune response to an infectious viral agent.