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Y Borel

Publications and source records attributed to Y Borel.

At least 55 records · Page 3Linked to original sources
PubMed1982

Communicative interactions between subpopulations of human T lymphocytes required for generation of suppressor effector function in a primary antibody response.

The cellular interactions necessary for generation of human T suppressor effector function were examined in a primary in vitro antigen-specific anti-DNP antibody-forming system. During the induction of the anti-DNP response, it was found that T cells of both T4+ and T8+ subsets were necessary to suppress antibody formation, whereas after activation, only the T8+ subset was required. Thus, a population of T4+ T cells appears to be necessary to activate or induce a subset of T8+ cells to suppress. The T4+ suppressor inducer population, like the resting or activated T8+ suppressor effector subset, was sensitive to low dose irradiation. Moreover, the radiosensitive T4+ subset and the previously defined T4+JRA+ subset were shown to be functionally similar or complementary in that both were required for generation of suppressor effector function. These findings suggest that T-T interactions between radiosensitive T4+JRA+ T cells and radiosensitive T8+ T cells are necessary for suppression of primary antigen-specific antibody production in man.

Antibody Formation↗
PubMed1981

Immune suppression to nucleosides: differences between NZB and NZW mice.

Previous studies (Y. Borel and M.C. Young, Proc. Natl. Acad. Sci. USA 1980 77: 1593) have shown that one can raise nucleic acid-specific suppressor T cells which diminish either the T-dependent immune response in vivo or the T-independent immune response in vitro. The results presented here confirm and extend these observations in several different strains of mice. Administration of nucleoside-modified spleen cells diminishes antibody-forming cells to nucleoside in mice immunized with nucleoside linked to keyhole limpet hemocyanin (KLH), Immune suppression was obtained in all strains except SJL and NZW, which are known to be high responders to denatured DNA. Both the primary and secondary immune responses were suppressed in C57BL/6 mice. Autologous cells exhibit a different ability to function as carriers. Spleen cells are the most effective, and to a certain extent, thymus cells. In contrast, bone marrow cells and red cells fail to induce immune suppression. A strain difference was found between NZB and NZW mice in their susceptibility to immunosuppression by nucleoside-modified spleen cells. Whereas NZB mice are high responders to nucleoside-KLH, they were easily suppressed by nucleoside coupled to spleen cells. In contrast, NZW mice, although relatively low responders to nucleoside-KLH, were not suppressed by administration of nucleoside coupled to spleen cells. Both male and female (NZB X NZW) F1 mice appeared to behave like the NZW parental strain and were resistant to immunosuppression by nucleoside-modified spleen cells. The significance of this observation for the pathogenesis of murine systemic lupus erythematosus is discussed.

Adenosine↗
PubMed1981

Autoantibody to an immunoregulatory inducer population in patients with juvenile rheumatoid arthritis.

The human inducer (T4(+)) and reciprocal cytotoxic/suppressor (T5(+)/T8(+)) subsets have been defined by monoclonal antibodies. In the present study, we examined the relationship of naturally occurring anti-T cell autoantibodies found in patients with active juvenile rheumatoid arthritis (JRA) to these subsets. In one approach, normal T cells were treated with anti-T4 or anti-T8 to eliminate the corresponding subset of cells and then analyzed for reactivity with JRA sera. It was found that JRA sera were reactive with only 15% of an enriched cytotoxic/suppressor population, whereas they reacted with 37% of an enriched inducer population. In reciprocal studies, JRA(+) T cells were eliminated with JRA sera and complement and the residual T cells (JRA(-)) reacted with monoclonal antibodies and indirect immunofluorescence on a fluorescence-activated cell sorter. As expected, the JRA sera and complement treatment of unfractionated T cells markedly diminished the T4(+) subset, whereas there was a concomitant increase in T cells reactive with anti-T5 and anti-T8. A similar diminution in T4(+) T cells was found in the circulating peripheral T cell compartment of patients with active JRA who possessed the JRA antibody. Functional studies demonstrated that removal of the JRA(+) population of T cells diminished phytohemagglutinin and soluble antigen proliferative responses, both of which were previously shown to be functions of T4(+) T cells. More importantly, in the absence of JRA(+) T cells, pokeweed mitogen-stimulated immunoglobulin production was markedly enhanced, despite the concomitant increase in T5(+)/T8(+) cytotoxic/suppressor cells. These results suggest that the JRA serum may define a Qal-like antigen found predominantly on the human inducer population which could activate suppressor and/or other feedback regulatory cells.

Antigens, Surface↗
PubMed1981

Prevention of tolerance induction by simultaneous administration of anti-Lyb3 antiserum with tolerogen.

Lyb3 serves as a triggering receptor on a mature subset of B lymphocytes. To further investigate the nature of the activating signal received by this receptor, we examined its involvement in hapten-specific B cell tolerance induced in vivo with isologous IgG. We obtained the following results: injection of anti-Lyb3 serum simultaneously with low doses of tolerogen prevented tolerance induction in B cells responsive to TD and TI type-1 antigens but failed to influence B cells responding to a TI type-2 antigen. Furthermore, administration of anti-Lyb3 serum did not change the tolerogenic signal to an immunogenic one, allowing B cell maturation into plaque-forming cells. However, it did make the B cell responsive to a subsequent challenge with antigen. This effect is transient, and dependent on the dose of tolerogen. These results are discussed in terms of our knowledge of the mechanism of B cell tolerance.

Animals↗
PubMed1981

The fine specificity of immune suppression to individual nucleosides.

The fine specificity of immune suppression was further studied in a murine experimental model in which the induction and expression of suppression by individual nucleoside-bound spleen cells were examined. The experiments were undertaken: a) to determine whether all 4 nucleosides have the ability to elicit suppressor T cells; b) to examine the specificity of cross-suppression induced by individual nucleosides; and c) to establish that nucleoside-specific suppression is mediated by T cells bearing nucleoside-specific receptors. The results show that, of the 4 nucleosides studied, only guanosine and thymine riboside were capable of eliciting immune suppression. Thymine riboside-coupled spleen cells induced cross-suppression to all 4 nucleosides. Furthermore, the nonresponsive state generated by guanosine-spleen cells was found to be transferable and mediated by nucleoside-binding T cells. The ability of only select nucleosides to elicit immune suppression is discussed in the context of recent evidence demonstrating the selective activation of T cell subsets by intramolecular antigenic determinants.

Animals↗
PubMed1980

Nucleic acid-specific suppressor T cells.

The concept of using cell-bound antigens as tolerogen was applied to nucleic acid. Nucleoside was linked directly to spleen cell suspensions. Intravenous administration of nucleoside coupled to isogeneic spleen cells into mice generated suppressor cells that diminished the formation of antibody-forming cells either to a T-dependent antigen in vivo or to a T-independent antigen in vitro. Suppressor cells were nucleoside specific, but the specificity of immune suppression seems to be somewhat broader than that of tolerance to a single nucleoside. The ability to raise nucleic acid-specific suppressor T cells may have implications for both the pathogenesis and treatment of systemic lupus erythematosus.

Animals↗
PubMed1980

Hapten-specific T-cell unresponsiveness induced bybenzylpenicilloyl autologous gamma globulin conjugates in human lymphocyes in vitro.

The aim of these studies was to determine whether unresponsiveness to the main determinant of penicillin, benzylpenicilloyl, can be induced in human peripheral lymphocytes in vitro by conjugates of benzylpenicilloyl (BPO) autologous gamma globulin (HGG). Initially it was shown that conjugates of BPO-keyhole limpet hemocyanin (KLH) elicited lymphocyte proliferation in the peripheral blood lymphocytes of six out of nine adult individuals in vitro. In contrast, conjugates of dinitrophenylated KLH and of BPO-HGG and the carriers HGG and KLH alone failed to do so. Similarly, release of the non-specific helper factor, lymphocyte mitogenic factor (LMF) occurred only after BPO-KLH stimulation. LMF activity was measured by B-cell proliferation and incorporation of radioactive amino acids into secreted immunoglobulin. Treatment with BPO-HGG for 24 h in vitro inhibited BPO-KLH-induced lymphocyte proliferation and LMF release. Treatment with either HGG, dinitrophenylated HGG, BPO-KLH, or BPO-human serum albumin failed to abrogate T-cell lymphocyte proliferation of human lymphocytes in vitro. The antigen specificity of the reduced immunologic responsiveness was further demonstrated by the observation that lymphocytes treated with BPO-HGG for 24 h in vitro responded normally to tetanus toxoid antigen.The data suggest that conjugates of BPO-HGG induce hapten-specific helper T-cell unresponsiveness in vitro.

Haptens↗
PubMed1980

The influence of hapten-conjugated isologous mouse gamma-globulin as a tolerogen on H-2 restricted cytotoxic effector cells.

Hapten-conjugated isologous mouse gamma-globulin (TNP-MGG) can induce specific unresponsiveness in spleen populations for primary antibody responses in vitro to both T-dependent (TNP-KLH) and T-independent (TNP-LPS) antigens. This was also tested simultaneously for its influence on spleen populations in the generation of cytotoxic effector cell populations to hapten-modified self. Unlike its effect on primary antibody responses (tolerogenic), TNP-MGG does not inhibit the generation of cytotoxic T cells against TNBS-treated syngeneic spleen cells. TNP-MGG was also unable to act as an immunogen in generating cytotoxic effectors against TNBS-treated spleen cells. These data show that although TNP-MGG has a tolerogenic effect on B lymphocytes (and possibly helper T lymphocytes) it does not block the generation of killer T lymphocytes directed against the hapten-modified spleen cells. A different mechanism of tolerance induction for TNP-MGG compared to hapten-modified syngeneic murine spleen is therefore suggested.

Animals↗
PubMed1979

Detection of antibody-forming cells and humoral antibody to horseradish peroxidase.

Two new simple methods for detecting antibody-forming cells by hemolytic plaque assay and hemagglutinating antibody to horseradish peroxidase have been developed in mice. Both techniques utilize as target, sheep erythrocytes coupled directly with horseradish peroxidase. These assays are sensitive, antigen-specific and are useful to quantitate both direct and indirect antibody-forming cells and humoral antibodies.

Animals↗