bluuebunny/crossref_metadata_2025 huggingface dataset:
Paradoxical effects of cyclosporin A on collagen arthritis in rats.
Authors: Kaibara N , Hotokebuchi T , Takagishi K , Katsuki I
Published: June 2004

The effect of the immunosuppressive agent cyclosporin A (CS-A) on collagen arthritis in Sprague-Dawley rats is investigated. A 14-d course of CS-A treatment at doses of 15 mg/kg per day or more, begun on the same day as type II collagen immunization, suppressed the development of arthritis as well as humoral and delayed-type hypersensitivity (DTH) skin test responses to type II collagen, possibly by interfering with helper T cells. Additional studies demonstrated that CS-A treatment only during the induction phase of immunity proved to be successful. When CS-A treatment was started only during the immediately preclinical phase of arthritis or after the disease onset, a significant enhancement of the disease was obtained in a dose-dependent manner. This enhancement was accompanied by an augmentation of DTH skin reactions, while antibody responses were either suppressed or unaffected. These results appear to be attributable at least in part to a suppressive effect of CS-A on a population of suppressor T cells, thus resulting in a T cell-mediated helper effect. It is therefore reasonable to assume that the paradoxical effects of CS-A on collagen arthritis in rats might be caused by an altering of the sensitive balance of the two regulatory subpopulations of T cells. It is also possible that cell-mediated immune responses may play an important role in influencing the course of the disease.
Interleukin 2 induces antigen-reactive T cell lines to secrete BCGF-I.
Authors: Howard M , Matis L , Malek T R , Shevach E , Kell W , Cohen D , Nakanishi K , Paul W E
Published: June 2004

Antigen-activated T lymphocytes produce within 24 h of stimulation a factor that is indistinguishable biochemically and functionally from the B cell co-stimulating growth factor, BCGF-I, originally identified in induced EL4 supernatants: Supernatants from antigen-stimulated T cell lines are not directly mitogenic for resting B cells, but synergize in an H-2-unrestricted manner with anti-Ig activated B cells to produce polyclonal proliferation but not antibody-forming-cell development; biochemical studies reveal the B cell co-stimulating factor present in antigen-stimulated T cell line supernatants is identical by phenyl Sepharose chromatography and isoelectric focusing (IEF) to EL4 supernatant BCGF-I. We thus conclude that normal T cells produce BCGF-I in response to antigenic stimulation. Analysis of the mechanism of BCGF-I production by antigen-stimulated T cells showed that optimum amounts of BCGF-I were obtained as quickly as 24 h post-stimulation, and that the factor producing cells in the T cell line investigated bore the Lyt-1+2- phenotype. As few as 10(4) T cells produced sufficient BCGF-I to support the proliferation of 5 X 10(4) purified anti-Ig activated B cells. Finally, the activation of normal T cell lines to produce BCGF-I required either antigen presented in the context of syngeneic antigen-presenting cells (APC) or interleukin 2 (IL-2).
Defective gamma interferon production in leprosy. Reversal with antigen and interleukin 2.
Authors: Nogueira N , Kaplan G , Levy E , Sarno E N , Kushner P , Granelli-Piperno A , Vieira L , Colomer Gould V , Levis W , Steinman R
Published: June 2004

Antigen and mitogen-induced gamma interferon (gamma-IFN) production was studied in peripheral blood mononuclear cells from 34 leprosy patients. 17 of 18 lepromatous leprosy and borderline lepromatous patients (LL and BL) failed to release gamma-IFN in response to specific antigen (Mycobacterium leprae) and displayed reduced responses to mitogen (concanavalin A) stimulation. In contrast, cells from six tuberculoid and borderline tuberculoid patients (TT and BT) produced considerable levels of gamma-IFN under the same experimental conditions. Normal controls failed to respond to M. leprae and most displayed good responses to concanavalin A. Mid-borderline patients (BB) showed intermediate levels of gamma-IFN release. gamma-IFN release by lepromatous patients could be partially restored with purified interleukin 2 and M. leprae antigen but not with interleukin 2 alone.
A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice.
Authors: Roths J B , Murphy E D , Eicher E M
Published: June 2004

A newly discovered autosomal recessive mutation, generalized lymphoproliferative disease (gld), in the C3H/HeJ strain of mice, determines the development of early onset massive lymphoid hyperplasia with autoimmunity. Significant lymph node enlargement is apparent as early as 12 wk of age. By 20 wk, lymph nodes are 50-fold heavier than those of coisogenic C3H/HeJ-+/+ mice. There is a concomitant increase in the numbers of peripheral blood lymphocytes. Analysis of C3H-gld lymph node lymphocyte subsets by immunofluorescence indicates an increase in numbers of B cells, T cells, and null (Thy-1-, sIg-) lymphocytes by 6-, 15-, and 33-fold compared with congeneic control mice. Serologically, gld/gld mice develop antinuclear antibodies (including anti-dsDNA), thymocyte-binding autoantibody, and hypergammaglobulinemia with major increases in several immunoglobulin isotypes. Mutant gld mice live only one-half as long as normal controls (12 and 23 mo, respectively). Interstitial pneumonitis was found in virtually all C3H-gld mice autopsied when moribund. Although immune complexes were detected in the glomerulus by immunofluorescence techniques, only 14% of the autopsied mice had significant lupus-like nephritis. Vascular disease was not found. The pattern of early onset massive lymph node enlargement, hypergammaglobulinemia, and production of antinuclear autoantibodies resembles the basic abnormal phenotype induced by the lpr (lymphoproliferation) mutation. The mutations gld and lpr are not allelic. Linkage studies indicate that gld is located between Pep-3 and Lp on chromosome 1. This new mutation adds another genetically well-defined model to the list of murine lymphoproliferative/autoimmune disorders that may be exploited to gain a clearer understanding of immunoregulatory defects and for identifying common pathogenetic factors involved in systemic autoimmune diseases.
Regulation of elastase and plasminogen activator secretion in resident and inflammatory macrophages by receptors for the Fc domain of immunoglobulin G.
Authors: Takemura R , Werb Z
Published: June 2004

We have determined that the interaction of IgG-coated erythrocytes (EIgG) and complement-coated erythrocytes (EIgMC) with macrophage Fc and complement receptors, respectively, modulates the secretion of the neutral proteinases, elastase, and plasminogen activator. EIgG binding and ingestion stimulated secretion of elastase and plasminogen activator less than or equal to 6-fold and 20-fold, respectively, over the 3 d following treatment. Stimulation was dependent on the IgG titer bound to each erythrocyte and was detectable at greater than 6.2 X 10(3) molecules IgG/ erythrocyte (total 0.99 nM IgG in the culture). Cytochalasin B did not inhibit stimulation, indicating that the ingestion of ligands was not necessary. Binding of EIgG to the three subclass-specific Fc receptors (IgG2a, IgG2b/IgG1, IgG3) was effective. Stimulation of elastase secretion required continued exposure of ligands to cells for up to 24 h, whereas production of plasminogen activator, which has plasma membrane-bound forms as well as secreted forms, was stimulated by exposure for 2 h. The stimulated production of elastase and plasminogen activator by triggering Fc receptors was seen only when the initial secretion rates were low. Periodate- or thioglycollate-elicited macrophages, which have high rates of proteinase secretion, were not stimulated further. EIgMC, which are bound but not ingested by resident macrophages, stimulated elastase secretion transiently, and the rate of secretion returned to the control level by 24 h. Therefore, the mode of stimulation of neutral proteinase secretion by complement receptor differed from that of Fc receptor; stimulation by complement receptor possibly involves a limited release of enzyme from intracellular stores, rather than stimulating accelerated synthesis of enzyme. Erythrocytes coated with both complement and IgG showed both the transient increase in elastase typical of complement-mediated secretion and the sustained increase typical of Fc receptor-mediated secretion. These results suggest that macrophage Fc and complement receptors regulate secretion of proteinases by receptor-specific mechanisms.
Spontaneous internalization of Class I major histocompatibility complex molecules in T lymphoid cells.
Authors: Tse D B , Pernis B
Published: June 2004

A low proportion of T lymphocytes in normal mouse spleen contains small intracytoplasmic vesicles showing Class I MHC molecules. After stimulation in vitro in a mixed lymphocyte reaction or by addition of Con A, the proportion of T cells with such intracytoplasmic vesicles increases progressively and becomes the majority. Labeling with fluorochrome-conjugated antibodies has shown that the vesicles are formed by internalization of molecules from the plasma membrane. The process is spontaneous and does not require cross-linking by antibodies or other ligands; it is selective inasmuch as other molecules (Thy-1 and T200 antigens) are not included and it is specific since it is not performed by other cells such as B lymphoid cells or fibroblasts. On the whole the process shows similarities with the internalization and recycling of other receptors, such as the receptors for different macromolecules of metabolic or informational significance, as seen in other cells. On the other hand, the specificity of Class I MHC mobilization in T lymphoid cells suggest a role for this process which is related to the immune function of these molecules.
Cloned LYT-2+ cytolytic T lymphocytes destroy allogeneic tissue in vivo.
Authors: Tyler J D , Galli S J , Snider M E , Dvorak A M , Steinmuller D
Published: June 2004

The long-accepted notion that alloimmune cytolytic T cells (CTL) mediate transplantation immunity has recently been called into question. In order to ascertain directly whether alloimmune CTL can mediate destruction of foreign tissue, we tested the ability of mouse CTL expanded as cloned populations in vitro to destroy allogeneic skin in vivo. The results of these studies prove unequivocally that cloned Lyt-2+ CTL can perform this task in an immunologically specific, H-2-restricted, and dose-dependent fashion.
The same human alloreactive T cell clone can help both B lymphocytes and specific cytotoxic precursors.
Authors: Ramarli D , Parodi B , Fabbi M , Corte G , Lanzavecchia A
Published: June 2004

Human alloreactive proliferating T cell clones have been compared for their capacity to provide help for B cell activation and the generation of a specific cytotoxic response. The results demonstrate that, when triggered by the relevant alloantigen, the same T cell clone can induce a strong polyclonal B cell activation and serve as the only source of helper cells for the generation of a specific cytotoxic response by any source of CTL precursors against any stimulator cell present in culture.
A reexamination of the role of LYT-2-positive T cells in murine skin graft rejection.
Authors: LeFrancois L , Bevan M J
Published: June 2004

We have investigated which T cell subclass defined by cytolysis with monoclonal anti-Lyt-1.2 and anti-Lyt-2.2 antibodies is required to adoptively transfer the ability to reject skin grafts. B6.Thy-1.1 spleen cells immune to graft antigens were fractionated with antibody plus C' and transferred to adult thymectomized, irradiated, bone marrow-reconstituted (ATXBM) B6.Thy-1.2 hosts that were simultaneously grafted with BALB.B skin. We found that when the ATXBM hosts were used 6 wk after irradiation and marrow reconstitution, both Lyt-1-depleted and Lyt-2-depleted immune spleen cells could transfer the ability to promptly reject skin grafts. However, such ATXBM recipients of Lyt-2-depleted cells that had rejected skin grafts were found to contain graft-specific CTL that were largely of host (B6.Thy-1.2) origin. When ATXBM hosts were used for the experiment 1 wk after irradiation and marrow reconstitution, no host-derived graft-specific CTL could be detected. However, graft rejection occurred in recipients of anti-Lyt-1- or anti-Lyt-2 plus C'-treated immune cells and specific CTL were generated from spleen cells of both groups. Thus, in the absence of a host-derived response, adoptively transferred immune Lyt-2+ cells, either resistant to, or that escaped from, antibody plus C' treatment, are able to expand in response to the antigenic stimulus provided by the graft. A more complete elimination of specific T cell subclasses is therefore needed to assess the relative contribution of a particular subset to the graft rejection process.
Analysis of the structural heterogeneity and polymorphism of human Ia antigens. Four distinct subsets of molecules are coexpressed in the Ia pool of both DR1,1 homozygous and DR3,W6 heterozygous B cell lines.
Authors: Accolla R S
Published: June 2004

Four monoclonal antibodies reacting with distinct human Ia antigenic determinants have been used to demonstrate the coexpression of four distinct subsets, NG1, NG2, H40+-3/4+, and DC1 H40--3/4+, in the Ia pool of DR heterozygous or homozygous B cell lines. By two-dimensional peptide mapping the four subsets within the same Ia pool displayed structurally different beta as well as alpha subunits. The beta chain of the NG1 subset was shown to display considerable structural polymorphism when analyzed in two cell lines with distinct DR but similar DC phenotype, LG2 (DR1,1-DC1) and Raji (DR3, W6-DC1). In contrast, the beta chains of NG2, DC1 H40+-3/4+, and DC1 H40--3/4+ subsets of LG2 cells were shown to be very similar to their homologous Raji cell counterparts, thus indicating a relatively low structural polymorphism. Furthermore, the alpha chains of either one of the four subsets expressed in LG2 cells displayed very high structural similarities to the homologous counterparts in the Raji Ia pool, thus suggesting a relatively low polymorphism for the large Ia subunits described in this study. A striking feature deduced from this study was the selective subunit association of the distinct alpha-beta heterodimers.
Thymic cytotoxic T lymphocytes are primed in vivo to minor histocompatibility antigens.
Authors: Fink P J , Bevan M J , Weissman I L
Published: June 2004

Potent cytotoxic T lymphocyte (CTL) activity can be derived from cultures of thymocyte responders and minor H different spleen cell stimulators. As is the case of the spleen cell response previously reported, this cytotoxic activity requires in vivo priming. We performed several experiments designed to determine whether the in vivo priming effect is due to the in situ priming of the thymocyte CTL precursors, to contamination of thymus cell preparations with cells of neighboring lymph nodes, or to the appearance in the thymus of antigen-reactive peripheral T cells. We show by depletion of peripheral cells with antilymphocyte serum and part body irradiation that recent thymic immigrants derived from the bone marrow contribute to the primed thymic response. Thymic CTL were primed in animals in which peripheral T cell responses were completely eliminated by repeated treatment in vivo with monoclonal anti-Thy-1 reagents. Primed, antigen-activated lymph node cells were also demonstrated to contribute to the thymus-derived CTL response. Thus, the minor H-specific thymic CTL response is due both to in situ priming and the immigration of activated peripheral T cells. We discuss the possible significance for models of T cell differentiation of the presence within the thymus of antigen and antigen-reactive mature T cells.
Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2.
Authors: Mazumder A , Rosenberg S A
Published: June 2004

In previous in vitro studies, we have shown that murine splenocytes or cancer patient lymphocytes incubated in IL-2 become lytic for fresh syngeneic or autologous tumors. We have now performed the adoptive transfer of such lymphokine-activated killer (LAK) cells in a murine B16 metastasis model to test their in vivo efficacy. 1 X 10(8) LAK cells, infused intravenously into C57BL/6 mice with established B16 pulmonary metastases, led to a marked decreased in the number of lung nodules and improved survival. LAK cells administered 3 d after amputation of a tumor-bearing limb also decreased the incidence of spontaneous pulmonary metastases. LAK cells generated from tumor-bearer splenocytes had effects equivalent to those from normal animals, and this antimetastatic effect of the LAK cells did not require the prior administration of cyclophosphamide or other immunosuppressants. Fresh or unstimulated splenocytes had no effect. The antitumor effectors and precursors in vivo and in vitro were Thy-1+. The lymphokine required for the activation appeared to be interleukin 2 (IL-2), since incubation in partially purified supernatants from PMA pulsed EL-4 or Con A-pulsed splenocytes or purified Jurkat IL-2 led to the generation of LAK cells equally active in vivo. The use of IL-2-activated cells may provide a valuable method for the adoptive therapy of human neoplasms as well.
Differences in the response of inbred mouse strains to the factor increasing monocytopoiesis.
Authors: Sluiter W , Elzenga-Claasen I , van der Voort van der Kley-van Andel A , van Furth R
Published: June 2004

Previous studies have shown that monocyte production during an inflammatory response is controlled by the factor increasing monocytopoiesis (FIM), secreted by macrophages at the site of inflammation. The inflammatory reaction to latex particles and a saline-soluble extract of Listeria monocytogenes (SEL), expressed as the number of monocytes in the circulation and of macrophages at the site of inflammation, was about twice as strong in C57BL/10 mice compared with CBA mice. This raised the question as to the mechanism underlying these differences. One possibility might be that these mouse strains differ with respect to the production of FIM, but this cannot be the case because the maximum levels of FIM activity in the serum of both C57BL/10 and CBA mice given latex or SEL intraperitoneally were almost the same; however, the courses of FIM activity in the two strains after intraperitoneal latex were not exactly synchronous. Another possibility is that the sensitivity of monocyte precursor cells for FIM differs. Evidence for the latter was provided by the finding that the intravenous injection of sera with FIM activity obtained from C57BL/10 and from CBA mice into the C57BL/10 mice evoked monocytosis, whereas CBA mice did not respond to these sera. Earlier studies showed that an increase of monocytes after the injection of serum containing FIM reflects increased monocyte production. Taken together, the results of the present study demonstrate that one of the mechanisms underlying the genetic control of the inflammatory response is, rather than enhanced FIM synthesis, the ability of monocyte precursors in the bone marrow to respond to FIM by increased monocyte production.
Monoclonal anti-Lyt-2.2 antibody blocks lectin-dependent cellular cytotoxicity of H-2-negative target cells.
Authors: Hünig T
Published: June 2004

The hypothesis that blocking of cytotoxic T lymphocyte (CTL)-mediated cytolysis with anti-Lyt-2 antibodies acts at the level of inhibiting the interaction of the Lyt-2-bearing structure with H-2 class I molecules was tested. In agreement with the findings of others, purified anti-Lyt-2.2 inhibited both antigen-specific lysis and lectin-dependent cellular cytotoxicity (LDCC). LDCC of H-2-positive and H-2-negative target cells was similarly inhibited by this antibody. As expected, this effect was specific for CTL expressing the Lyt-2.2 allele, in contrast to blocking with a rat monoclonal antibody to the murine LFA-1 antigen. The implications of this finding for the function of the Lyt-2 antigen in CTL-target cell interaction are discussed.
High frequency of lambda gene activation in bone marrow pre-B cells.
Authors: Nishikawa S I , Kina T , Gyotoku J I , Katsura Y
Published: June 2004

The frequency of lambda light chain (L) producing cells in immunoglobulin-producing cells that have been generated in vitro from bone marrow pre-B cells was investigated. The frequency of lambda-producing cells obtained in such a culture was three- to eightfold higher than that observed in the culture of mature spleen B cells. These results suggest that the activation of lambda gene at pre-B cell stage occurs far more frequently than the frequency presumed from the percentage of lambda-bearing cells in mature B cells.
T cell-activating properties of an anti-Thy-1 monoclonal antibody. Possible analogy to OKT3/Leu-4.
Authors: Gunter K C , Malek T R , Shevach E M
Published: June 2004

We have identified a single rat monoclonal antibody, G7, that is a potent inducer of interleukin (IL-2) production from all functioning T cell hybridomas as well as from normal T cells. G7 is also mitogenic for normal T cells and is a very effective inducer of IL-2 receptor expression. On fluorescence-activated cell sorter analysis, G7 recognized a pan-T cell antigen. Immunoprecipitation studies demonstrated that G7 recognized a cell surface molecule of 28-32 kD that appeared to be identical to Thy-1 in coprecipitation studies. In addition, G7 precipitated a protein of 50 kD. The possible relationship of the putative molecular complex identified by G7 on murine cells to the molecular complex identified on human T cells with anti-T3 reagents is discussed. In addition, G7 should prove to be a very useful reagent for studying the early events of lymphocyte activation as well as an inducer of lymphokine-rich supernatants.
Evidence for gene conversion among immunoglobulin heavy chain variable region genes.
Authors: Clarke S H , Rudikoff S
Published: June 2004

We have previously reported that the VH region amino acid sequence of a phosphocholine (PC)-binding hybridoma antibody of CBA/J origin, HP101 6G6 (6G6), differs extensively from the VH regions of other PC-binding antibodies. The sequence of 6G6 VH appears to be derived from a gene homologous to the BALB/c V11 gene, a member of the PC VH (T15 VH) gene family not normally used to encode PC-binding antibodies. The 6G6 VH sequence differs from the translated sequence of V11 by six amino acids, four of which occur at the same position in other members of this gene family. This coincidence led to the proposal that the 6G6 VH gene was derived by gene conversion involving three genes of the PC VH gene family. We report here the nucleic acid sequence of the rearranged VH gene of hybridoma 6G6. This sequence supports our previous suggestion of gene conversion by confirming those differences, relative to the BALB/c V11 gene sequence, that are encoded by other members of this gene family, and extends this correlation to include three silent base pair substitutions as well. In addition, 5' noncoding region sequence and Southern blot analysis using probes derived from the coding and 5' noncoding regions confirm that the 6G6 VH gene is likely to be derived from the V11 homologue in CBA/J mice, and suggest that all three genes believed to be involved in the generation of the 6G6 VH gene are present in the CBA/J genome, a prerequisite for their involvement in gene conversion.
Isotype specificity of helper T cell clones. Peyer's patch Th cells preferentially collaborate with mature IgA B cells for IgA responses.
Authors: Kiyono H , Cooper M D , Kearney J F , Mosteller L M , Michalek S M , Koopman W J , McGhee J R
Published: June 2004

The nature of the IgA B cell precursors that receive preferential help from selected clones of T helper cells from mouse Peyer's patches (PP Th A) were studied. Activation of the PP Th A clones required the presence of antigen, sheep erythrocytes (SRBC), in a culture system supporting development of antibody-secreting plasma cells. Two types of PP Th A cells were used. Both gave vigorous IgA responses; the first also supported low IgM, and the second low IgM and IgG subclass antibody responses. Removal of sIgA+ B cells from either splenic or PP B cell cultures selectively depleted precursors of IgA antibody producers. Cultures of purified sIgA+ B cells, cloned PP Th A cells and SRBC, selectively yielded IgA antibody producers. Finally, PP Th A cells did not support IgA responses in B cell cultures derived from spleens of young mice (days 1-25), and full IgA responses were not seen until the donor mice were 6-7 wk of age. These results suggest that cloned T helper cells can recognize and collaborate with mature, IgA committed B cells.
Involvement of the K and I regions of the H-2 complex in resistance to hemopoietic allografts.
Authors: Drizlikh G , Schmidt-Sole J , Yankelevich B
Published: June 2004

Irradiated (H-2b X H-2k)F1 and (H-2b X H-2d)F1 recipients strongly resist the growth of H-2b parental bone marrow cells and do not resist marrow grafts from non-H-2b parents such as C3H and BALB/c. This phenomenon of hybrid resistance has been shown to be under genetic control of the H-2D-linked loci and was interpreted by Cudkowicz (9) as due to the existence of H-2D-linked recessive hemopoietic histocompatibility genes. To check whether the H-2D-linked loci are solely responsible for the fate of bone marrow allografts, we measured the strength of resistance of irradiated (B6 X C3H)F1 and (B6 X BALB/c)F1 recipients toward bone marrow grafts from a set of H-2 recombinant and F1 hybrid donors carrying either the H-2b, H-2d, and H-2k alleles. We found that growth of all H-2b grafts was resisted, although to different degrees. Resistance was minimal when donors shared with the input strain of a corresponding F1 hybrid the H-2K and H-2I regions, or when both F1 donors and F1 recipients formed identical unique hybrid Ia molecules. In addition, H-2b grafts were resisted by congenic, H-2D-identical, H-2K-and H-2I-incompatible recipients. The fate of grafts from H-2Dd donors seemed to depend on the incompatibility of the combinatorial determinant Ia.22. If both donor and recipient expressed such a determinant (either in the cis or in the transposition), or if neither could form such a determinant, grafts were not resisted. The H-2Dk allele is not the main or only factor that confers on the C3H parental bone marrow cells the ability to grow unresisted in (B6 X C3H)F1 recipients. Grafts from congenic C3H.OH donors, carrying the same H-2Dk alleles and differing in the left part of the H-2 complex, were resisted by the F1 recipients. We conclude that both class I (K and D) and class II (I-A and I-E) major histocompatibility complex genes, rather than hypothetical hemopoietic histocompatibility genes control hemopoietic resistance. To reconcile codominant inheritance of classic H-2 antigens with the apparent recessive inheritance of hybrid resistance, we assume that there exist parental determinants that are not formed in some F1 hybrids due to preferential association of either Ia alpha chains with allogeneic beta chains or of class I antigens with allogeneic or hybrid class II restriction elements.
An idiotype-specific helper population that bears immunoglobulin, Ia, and Lyt-1 determinants.
Authors: Sherr D H , Dorf M E
Published: June 2004

A helper cell population with phenotypic characteristics of both B and T cells is described. This helper population, called BH, is present in normal unprimed C57BL/6 mice and preferentially helps the expression of NPb idiotype-bearing plaque-forming B cells in the absence of T helper cells. Its surface phenotype is Lyt-1.2+, Ig+, Lyb-3+, Thy-1.2-, Lyt-2.2-. The helper activity of the BH population is IgH restricted and BH cells selectively bind NPb idiotypic determinants. Collectively the data demonstrate that this unique subpopulation can regulate the response of antibody-secreting B cells through specific recognition of idiotypic determinants.
Common protective antigens of group A streptococcal M proteins masked by fibrinogen.
Authors: Whitnack E , Dale J B , Beachey E H
Published: June 2004

The influence of fibrinogen on the opsonization of Group A streptococci by type-specific and cross-reactive anti-M protein antisera was investigated. As previously reported for type 24 streptococci, fibrinogen inhibited the complement-mediated opsonization of types 5, 6, and 19 organisms. Rabbit antisera against large peptide fragments of purified homologous M proteins (pep M proteins) overcame the anti-opsonic effect of fibrinogen in a dose-dependent manner. In the presence of optimal amounts of antibody, bacterial uptake by PMN was equal in serum and plasma, and greater than could be obtained in serum in the absence of antibody. Polyclonal anti-pep M sera contained antibodies directed against fibrinogen-binding as well as fibrinogen-nonbinding sites or regions of the M protein molecule. Three cross-reactive anti-pep M sera included antibodies directed against fibrinogen binding sites or regions of the cross-reacting M proteins. In the two sera studied in detail, these antibodies accounted for a large part of the cross-reacting anti-M antibody present in the sera. We suggest that fibrinogen binding sites on different serotypes of M protein may be structurally and therefore antigenically similar. Conservation of fibrinogen binding sites on M proteins may be related to their protective anti-opsonic function.
Functional and biochemical studies of multinucleated giant cells derived from the culture of human monocytes.
Authors: Schlesinger L , Musson R A , Johnston R B
Published: June 2004

We compared phagocytic and metabolic activities of multinucleated giant cells (MGC) and macrophages derived from human monocytes after 9-14 d in culture. Phagocytosis of sheep erythrocytes (E) coated with IgG, of E coated with IgM and complement, and of Candida albicans was comparable in MGC and macrophages. The same percentage of ingested fungi was killed by MGC (24 +/- 4%) and macrophages (21 +/- 5%). Approximately 70% of MGC and macrophages exhibited superoxide-dependent reduction of nitroblue tetrazolium during stimulation. Ia antigen was present on approximately 75% of both cell types. Analysis of cell populations separated by nuclear fluorescence indicated that beta-glucosaminidase, acid phosphatase, and beta-glucuronidase activity per cell was higher in MGC, but specific activity of these enzymes was greater in macrophages. These results suggest that MGC have the capacity to function like macrophages in host defense against infection.
Generation and decay of the immune response to a progressive fibrosarcoma. I. Ly-1+2- suppressor T cells down-regulate the generation of Ly-1-2+ effector T cells.
Authors: North R J , Bursuker I
Published: June 2004

It was shown that the progressive growth of the immunogenic meth A fibrosarcoma in its semisyngeneic host results in the generation of concomitant immunity to the growth of a tumor implant. The generation of immunity occurred between days 6 and 9 of tumor growth and was associated with the generation of sensitized T cells that were capable, on passive transfer, of causing regression of a 3-d tumor in gamma-irradiated recipients. After day 9 of tumor growth, concomitant immunity and the T cells able to passively transfer it were progressively lost, and this was associated with the generation of splenic suppressor T cells able to suppress the expression of adoptive immunity against an established tumor in T cell-deficient ( TXB ) recipients. The T cells that passively transferred concomitant immunity were shown to be of the Ly-1-2+ phenotype, in contrast to the T cells that transferred suppression, which were shown with the same reagents to be Ly-1+2-. The results are consistent with the hypothesis that the progressive growth of an immunogenic tumor results in the generation of Ly-1-2+-sensitized effector T cells that fail to reach a number sufficient to destroy the tumor because their generation is down-regulated by tumor-induced Ly-1+2- suppressor T cells.
Gonococcal pili. Primary structure and receptor binding domain.
Authors: Schoolnik G K , Fernandez R , Tai J Y , Rothbard J , Gotschlich E C
Published: June 2004

The complete amino acid sequence of pilin from gonococcal strain MS11 and the sequence of constant and variable regions from strain R10 pilin have been determined in order to elucidate the structural basis for adherence function, antigenic diversity, and polymeric structure. The MS11 pilin sequence consists of 159 amino acids in a single polypeptide chain with two cysteines in disulfide linkage and serine-bonded phosphate residues. TC-2 (31-111), a soluble monomeric pilus peptide prepared by arginine-specific digestion, bound human endocervical, but not buccal or HeLa cells and therefore is postulated to encompass the receptor binding domain. Variable regions of CNBr-3 appear to confer antigenic diversity and comprise segments in which changes in the position of charged residues occur in hydrophilic, beta-turns. Residues 2-21 and 202-221 of gonococcal pilins and lower eucaryotic actins, respectively, exhibit 50% homology. When these residues are arranged at intervals of 100 degrees of arc on "helical wheels," the identical amino acids comprise a hydrophobic face on one side of the helix. This observation, the hydrophobic character of this region and the tendency for TC-1 (residues 1-30) to aggregate in water, suggest that this stretch interacts with other subunits to stabilize polymeric structure.
Mechanisms of Ly2 suppressor cell activity. Activation of an Ly1 I-J+ cell is required to transduce the suppressive signal.
Authors: Flood P M , Louie D C
Published: June 2004

A cell-free product secreted by Ly1-2+ T cells (Ly2 TsF) can suppress the in vitro response to sheep erythrocytes (SRBC) of spleen cells depleted of Ly2+ T cells. This suppressor factor expresses biological activity only when the acceptor cells share major histocompatibility complex (MHC)-linked polymorphic genes with the cells that made the Ly2 TsF. Removal of Ly1 I-J+ cells from the assay culture abrogates the ability of Ly2 TsF to suppress these cultures, but we can replace the need for the I-J+ cells in the assay culture with an I-J+ soluble factor derived from them. We investigated the cellular interactions involved in the activation of I-J+ cells by Ly2 TsF in vitro. We have been able to induce the production of an I-J+ molecule needed for Ly2 TsF activity in a 48-h intermediate culture of B cell-depleted Ly1 spleen cells, Ly2 TsF, and antigen. This molecule not only fails to bind antigen, but is also antigen nonspecific in that it can be induced by Ly2 TsF of irrelevant specificities. In order to replace the activity of the Ly1 I-J+ cell in the assay culture, the cell induced by Ly2 TsF to produce the I-J+ molecule in vitro must share genetic polymorphisms linked to the MHC with the Ly2 TsF, and genetic polymorphisms linked to the Igh-V gene complex with the target cell. In order for Ly2 TsF to induce cells of the primary culture to produce the I-J+ molecule, Ly2 TsF must share genetic polymorphisms linked to the IE region of the MHC with the Ly1 I-J+ cell producing the I-J+ molecule. These results indicate that the suppressive mechanism of Ly2 TsF involves the interaction with an Ly1 I-J+ molecule. This I-J+ molecule serves to focus the antigen-specific suppressor molecule on the target cell. The recognition event of this suppressive complex on the surface of the acceptor cell is controlled by Igh-V-linked genes restricted by the I-J+ molecule of the suppressor complex. This suppressor interaction is confined to the suppressor effector phase of the suppressor circuit since the I-J+ molecules needed for by Ly2 TsF activity do not substitute for the I-J+ molecules needed for the activity of Ly1 TsiF , a T cell factor that initiates the suppressor cell circuit.(ABSTRACT TRUNCATED AT 400 WORDS)
Trinitrophenyl modification of H-2k and H-2b spleen cells results in enhanced serological detection of Kk-like determinants.
Authors: Levy R B , Dower S K , Shearer G M , Segal D M
Published: June 2004

Several anti-H-2Kk but not anti-H-2Dd monoclonal antibodies (mAb) exhibited enhanced binding to B10.A murine spleen cells after modification of the cells with trinitrobenzene sulfonate (TNBS). The number of antibody molecules bound to TNP-modified B10.A spleen cells increased by a factor of two or more. The same anti-2Kk mAb that exhibited enhanced binding to modified B10.A cells did not bind to unmodified C57BL/10 spleen cells, as expected, but did bind to TNP-modified C57BL/10 spleen cells. This TNP-dependent binding was not a result of cross-reactions with cell surface TNP groups nor with Fc receptors. TNP modification of a variant cell line that does not express class I H-2 products did not result in enhanced binding by these mAb. These findings can account for preferential recognition of TNP-Kk by B10.A and B10.BR CTL, and also for cross-reactive lysis by C57BL/10 CTL stimulated by C57BL/10-TNP against unmodified H-2Kk targets.
Effect of ingested sperm on fecundity in the rat.
Authors: Allardyce R A
Published: June 2004

The intragastric administration of homologous strain epididymal sperm to adult virgin NZBW (Rt 1) female rats was shown to induce short-to long-term infertility. Infertility was associated with an early rise of genital secretory fluid IgA antisperm antibody preceding mating.
Soluble factor requirements for the autostimulatory growth of B lymphoblasts immortalized by Epstein-Barr virus.
Authors: Gordon J , Ley S C , Melamed M D , Aman P , Hughes-Jones N C
Published: June 2004

B lymphoblasts immortalized by the Epstein-Barr virus (EBV) exhibit autocrine growth stimulation--that is they release a soluble activity to which they respond by growth. A minimally supplemented serum-free medium conditioned by lymphoblastoid cells in their log phase of growth (LCL-CM) was found to contain autostimulatory activity allowing us to explore the mechanism of autocrine growth for these cell-types in defined conditions. Below cell densities capable of supporting autonomous growth, continued proliferation in serum-free medium was dependent on both added LCL-CM and transferrin. Neither activity alone was capable of sustaining growth. At higher cell densities, transferrin by itself was sufficient to maintain the autocrine loop. The action of the autostimulatory factor appeared to reside in its ability to prime cells continually for a proliferative response to transferrin by enhancing the expression of transferrin receptors at the lymphoblast surfaces. The implications of these findings for normal B cell physiology and their possible relation to oncogenesis are discussed.
Identification of a unique erythroleukemia-associated retroviral gp70 expressed during early stages of normal erythroid differentiation.
Authors: Britt W J , Chesebro B , Portis J L
Published: June 2004

Late in the course of Friend virus (FV)-induced erythroleukemia, leukemic spleen cells express a cell surface retroviral gp70 envelope protein not detected during the early proliferative phase of the disease. Characterization of this gp70 revealed it was unrelated to the input Friend murine leukemia virus (F-MuLV), but antigenically similar to a unique subset of endogenous xenotropic viruses. This gp70 was expressed by murine erythroleukemia cell lines but has not been identified on cell lines of other lineages. A monoclonal antibody (18-6) specifically reactive with this polypeptide was used to examine hematopoietic organs of normal uninoculated mice. This antibody detected a gp70 expressed by a majority of erythroid cells in fetal liver and by a small but significant percentage of normal adult spleen and bone marrow cells. Increased erythropoietic activity induced by treatment of adult mice with phenylhydrazine ( PHZ ) resulted in a seven- to eightfold increase in the frequency of spleen and bone marrow cells expressing this gp70. Peptide map analysis indicated that the 18-6 reactive gp70 expressed by Friend erythroleukemia cells and by cells from normal fetal liver were structurally identical. These results suggested that this unique gp70 was an erythroid-specific differentiation antigen.
T cell surface I-J glycoprotein. Concerted action of chromosome-4 and -17 genes forms an epitope dependent on alpha-D-mannosyl residues.
Authors: Klyczek K K , Cantor H , Hayes C E
Published: June 2004

Two genes acting in concert control murine T cell I-Jk expression. We determined I-Jk expression with I-Jk--specific monoclonal antibodies WF8 .C12.8 and five others produced in our laboratory in a cytotoxicity assay. Previous experiments established that an H-2k gene and a chromosome 4 gene, Jt , regulate I-Jk expression. We show here that B10. HTT and B10.S( 9R ) do not differ at the H-2k locus required for I-Jk expression. Rather B10. HTT , like B10.A(3R), lacks some important non--H-2 gene (possibly Jt ). The intra--H-2k I-J--controlling locus maps to the right of the I-A subregion. The I-Jk determinant involves a carbohydrate structure associated with protein; inhibiting either protein synthesis or glycosylation prevents T cell I-Jk reexpression after proteolytic removal. Treatment with alpha-mannosidase destroys I-Jk determinants, implicating terminal alpha-D-mannosyl residues in the I-Jk epitope. Models for H-2 and Jt control of I-J expression are discussed.
Effects of beta interferon on human fibroblasts at different population doubling levels. Proliferation, cell volume, thymidine uptake, and DNA synthesis.
Authors: Jasny B R , Pfeffer L M , Tamm I
Published: June 2004

Cellular aging had no effect on the ability of beta interferon to increase cell volume and population doubling time in 76-109 cells, a line of human skin fibroblasts. However, DNA synthesis in cells at high population doubling levels (PDL 55-70) was inhibited after 72 h of beta interferon treatment (1,000 U/ml) while no inhibition of DNA synthesis was observed in cells at middle population doubling levels (PDL 30-40).
Activation of B lymphocytes by monovalent anti-Lyb-2 antibodies.
Authors: Subbarao B , Mosier D E
Published: June 2004

Although activation of B lymphocytes by antigen or anti-Ig antibody has been shown to require cross-linking of surface Ig molecules, cross-linking is not necessary for B cell activation by anti-Lyb-2 monoclonal antibody (MAb). Monovalent Fab' fragments of anti-Lyb-2 MAb are as effective as the intact antibody in inducing blast cell transformation of small B cells and B cell proliferation in the apparent absence of T cells and adherent cells. In the presence of factors from T cells, B cells activated by Fab' fragments of anti-Lyb-2 MAb were induced to mature into Ig-secreting cells. Since monovalent Fab' fragments probably cannot induce receptor aggregation, it appears that receptor occupancy is sufficient to induce B cell activation with anti-Lyb-2 MAb.
Negative selection in vivo reveals expression of strong Mls determinants in mice with X-linked immunodeficiency.
Authors: Webb S R , Mosier D E , Wilson D B , Sprent J
Published: June 2004

Evidence is presented that mice with X-linked immunodeficiency (xid) express strong Mlsa,d determinants, a putative marker of the mature subset of B cells. Although young (3-5 wk) (CBA/N X DBA/2)F1 male (xid+) mice stimulated only very weak mixed lymphocyte reactions (MLR) to Mlsa,d determinants, older mice (greater than 7 wk) regularly elicited conspicuous responses, despite being totally unresponsive to TNP-Ficoll. Expression of Mlsa,d determinants by xid+ mice was also detected by the procedure of negative selection in vivo. Thus BALB/c T cells were totally depleted of Mlsa,d reactivity after blood to lymph recirculation through 10-wk old irradiated xid+ (CBA/N X DBA/2)1 male mice. Significantly, a marked (90%) reduction in the anti-Mlsa,d response also occurred with T cell filtration through 3-wk xid+ mice, i.e., mice that elicit only minimal primary MLR; filtration through 3-wk xid- normal female mice led to near-complete (99%) negative selection. Collectively these data indicate either, (a) that xid+ mice contain appreciable numbers of cells with at least some of the properties of mature B cells, or (b) that the expression of Mlsa,d determinants is not restricted to mature B cells. In either case, B cells from xid mice cannot be viewed as a simple model for immature normal B cells.
Gut mucosal mast cells. Origin, traffic, and differentiation.
Authors: Guy-Grand D , Dy M , Luffau G , Vassalli P
Published: June 2004

Gut mucosal mast cells (MMC), which are nearly absent in normal mice are abundant during nematode infection. In normal mice, study of MMC precursors (MMC-P: cells giving rise to MMC colonies in the presence of IL-3) show that: (a) their frequency, judged by limiting dilution is very high in bone marrow (BM) and gut, and very low in most lymphoid organs and thoracic duct lymph (TDL); (b) gut MMC-P are Thy-1- Lyt-1-2- and are not rapidly replicating; (c) they are the progeny of less differentiated BM MMC-P which are attracted from the blood to the gut mucosa by local factor(s), other than antigen and T cell factors (since normal amounts of gut MMC-P are found in germ-free, nude, and newborn mice). In mice bearing the Wehi 3 tumor (which releases enough IL-3 to produce detectable blood levels) spleen and mesenteric lymph nodes (LN) show increased MMC-P frequency, the greatest increase being in the gut and BM, where numerous differentiated MMC are found. In Nippostrongylus brasiliensis (Nb)-infested mice (known to develop a large, T cell-dependent, gut MMC infiltration), gut MMC-P proliferation is induced by IL-3 released from gut mucosal Thy-1+ Lyt-2- cells, whose in vitro IL-3 release capability is much higher than that of similar cells from normal mice. Both Nb-stimulated T blasts and proliferating MMC-P undergo cyclic traffic, migrating into the TDL and then seeding the whole length of the gut (a process which allows a widespread immune defense after a local antigenic stimulus). Experiments using 2-d interruption of this traffic and fetal gut grafts, suggest that the continuous homing of T blasts back to the gut which leads to permanent Nb-stimulated IL-3 release, is essential for the full maturation of MMC. Transfer experiments in the rat show that TDL circulating MMC-P rapidly mature into MMC when they home back to the Nb-infested gut. It is proposed that gut MMC arise after several stages of progressive differentiation of MMC-P, influenced both by IL-3 and unidentified gut factor(s).