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Biomedical subjects

B Benacerraf

Publications and source records attributed to B Benacerraf.

At least 127 records · Page 7Linked to original sources
PubMed1982

I-J-restricted interactions in the generation of azobenzenearsonate-specific suppressor T cells.

The genetic restrictions of the activation of third-order suppressor cells (Ts3) were studied in mice, using two different types of anti-azobenzenearsonate (ABA)-immune responses, namely delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) generation. Ts2 cells were induced in several different strains of mice by injecting monoclonal T hybridoma molecules or first-order suppressor factors (TsF1) originating in A/J (H-2a, Igh-1e) mice and then testing the TsF2 molecules derived from these Ts2 in A/J and A.By (H-2b, Igh-1e) or (A/J X A.By)F1 (H-2a/b, Igh-1e) and (C57Bl/6 X A/J)F1 (H-2b/a, Igh-1e) mice. It was shown that the activity of TsF2 was restricted to the I-J of the strain in which Ts2 was induced. By genetic analysis, restriction was shown to be due to the requirement of H-2 identity between ABA-coupled cells used for Ts3 activation and the strain of the TsF2 origin. Moreover, by using H-2-congenic ABA-coupled cells, we were also able to precisely map and demonstrate that ABA-coupled cells I-J identical to TsF2 induced in various strains were necessary for effective suppression to occur. This selective activation of Ts3 suggested the existence of I-J-related antigen presentation for suppression as the counterpart of I-A or I-A-I-E-restricted antigen presentation for positive immune responses.

Animals↗
PubMed1982

Two distinct mechanisms regulate the in vivo generation of cytotoxic T cells.

Treatment of responder cells with monoclonal anti-Ly-1,2 antibodies plus complement in vitro completely eliminated their ability to generate azobenzenearsonate (ABA)-specific cytolytic T lymphocytes (CTL). However, addition of the concanavalin A-stimulated supernatants of rat spleen cells (Con A-Sup) can fully reconstitute the response. Therefore, Lyt-1,2-bearing T cells are required for the generation of ABA-specific CTL, and such requirement can be replaced by factors present in the Con A- sup. Suppressor T cells (Ts), when adoptively transferred into naive recipients, will inhibit the in vivo priming of CTL. This inhibition can also be reversed by in vitro addition of Con A-Sup. furthermore, mice serving as donors of Ts also show profound unresponsiveness when primed and restimulated in vitro. In contrast to the Ts-mediated inhibition, in vitro addition of Con A-Sup was unable to abolish the unresponsiveness observed in these cultures. Thus, we identified two unresponsive states in a hapten-specific killing system that differ in their ability to be reconstituted by Con A-Sup.

Animals↗
PubMed1982

In vitro generation of helper T cells and suppressor T cells that regulate the cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells.

Helper T cells and suppressor T cells have been generated in vitro that regulate the cytolytic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified syngeneic cells. B6D2F1 helper cells generated to TNP-modified parental (P1) cells augment the CTL response to those P1-TNP-modified antigens but not to P2-TNP-modified antigens. The generation of these helper T cells requires the presence of splenic adherent cells and these helper T cells are radioresistant. A soluble factor can be obtained from the helper T cell cultures that can also augment the CTL response. The suppressor T cells generated in culture do not demonstrate the specificity observed with the helper T cells; however, they are antigen-dependent in their induction. Whether helper or suppressor activity is obtained depends upon the length of time cells are cultured in vitro.

Animals↗
PubMed1982

Genetic control of the cytolytic T lymphocyte response to influenza viruses: H-2 genes influence the response to H-2Kb plus virus.

Genetic control of the cytolytic T lymphocyte responses to influenza virus was examined. Mice bearing the H-2b haplotype and F1 hybrid mice derived from C57BL/6 parents failed to recognize H-2Kb plus type A or type B influenza viruses. Congenic mice that shared H-2Kb but had either H-2Dd of H-2Dq genotypes responded in in vitro secondary cultures to H-2Kb plus virus. Mapping studies suggest the gene(s) controlling the ability to respond to H-2Kb plus virus can be localized in or near the H-2D region. Several interpretations of these observations are discussed.

Animals↗
PubMed1982

Antigen- and receptor-driven regulatory mechanisms. X. The induction and suppression of hapten-specific granulomas.

We have investigated the induction and suppression of granuloma formation elicited by the azobenzenearsonate (ABA) determinant in A/J Mice. ABA-derived syngeneic spleen cells (ABA-SC) administered subcutaneously induced hapten-specific delayed hypersensitivity (DTH), detected by footpad swelling, upon challenge with ABA-bovine serum albumin (BSA) coupled to polyacrylamide beads (PAB). The reactions elicited by ABA-BSA-PAB reached maximal intensity at 24 hours but were relatively persistent and were still marked at 96 hours. Histopathologic examination of footpad responses at 24 and 48 hours after challenge revealed compact collections around beads of mononuclear cells and granulocytes, which were characteristic of DTH reactions. Discrete epithelioid granulomas became apparent by 72 or 96 hours. Unprimed mice or mice primed with ABA-SC and challenged with uncoupled beads did not develop either substantial leukocytic infiltrates or granulomas. Persistent delayed responses were only apparent if the mice were challenged with the homologous hapten-coupled bead, indicating the fine specificity of the reaction. Immune cells were shown to be capable of transferring DTH and granulomatous responsiveness to ABA; the cells were sensitive to anti-Thy 1.2 antiserum and complement, which indicates that the response was thymic-dependent. The intravenous injection of ABA-SC, which is known to induce suppressor cells, prevented the development of DTH or granulomatous responsiveness followinggg subcutaneous immunization with ABA-SC. In addition, the transfer of suspensions containing suppressor T cells into syngeneic mice primed with ABA-SC prevented the development of DTH reactions and granuloma formation followin challenge with ABA-BSA-PAB. Furthermore, only hapten-specific suppressor T cells limited persistent delayed hypersensitivity responses. Having successfully developed granulomas in the footpad, the authors induced and suppressed granulomatous lesions in the gastrointestinal tract in a similar fashion. These experiments establish a model in inbred mice for the study of granulomatous diseases, including those of the gastrointestinal tract.

Animals↗
PubMed1982

Biologic activity of an idiotype-bearing suppressor T cell factor produced by a long-term T cell hybridoma.

Biologic activities and immunochemical characteristics of an azobenzenearsonate- (ABA)specific suppressor T cell factor produced by a longterm T cell hybridoma, F12, were studied. In vivo administration of F12 culture supernatant resulted in the suppression of ABA-specific delayed-type hypersensitivity (DTH) responses and the inhibition of priming for ABA-specific cytotoxic T lymphocyte responses. Moreover, F12 induced a second set of suppressor cells that act in the efferent phase of DTH. The active material in the F12 culture supernatant expressed major cross-reactive idiotypic (CRI) determinants of anti-ABA antibodies of A/J mice and I-J subregion-coded specificities but not express determinants of immunoglobulin constant regions. These results demonstrated that F12 is a functioning hybrid cell line of the first-order suppressor T cell subset.

Animals↗
PubMed1982

Hapten-coupled monoclonal anti-I-A antibodies provide a first signal for the induction of suppression.

A mechanism for induction of hapten-specific immune unresponsiveness is described that utilizes a hapten-conjugated monoclonal anti-Ia antibody to direct the in vivo immune response. Azobenzenearsonate- (ABA) coupled anti-I-Ak antibodies provide a potent first signal for the induction of nonresponsiveness to ABA in H-2k,a mice. The use of an anti-Ia antibody requires haplotype matching and may selectively direct the hapten signal, because other haptenated monoclonal antibodies are ineffective. There is an absolute requirement for a second signal to achieve in vivo suppression; the signal may be substituted by the generation of an allogeneic effect at the time of hapten presentation. We suggest that these methods allow for specific targeting of hapten-suppressive signals that differ considerably from other model systems of tolerance to haptenated immunoglobulins. The results are discussed in relation to a potential role for an Ia+ cell involved in the induction of regulating suppressor pathways.

Animals↗
PubMed1981

Analysis of T cell hybridomas. I. Characterization of H-2 and Igh-restricted monoclonal suppressor factors.

Five hybridoma T cell lines were prepared by fusion of second order suppressor T cells (Ts2) with the BW5147 thymoma. The culture supernates from these T cell hybrids contained a factor, TsF2, which specifically suppressed 4-hydroxy-3-nitrophenyl acetyl hapten (NP)-induced cutaneous sensitivity responses. TsF2 activity was observed when the factor was administered during the effector phases of the immune response. TsF2 bears I-J determinants and has binding specificity for NPb idiotypic determinants. TsF2 suppressor activity could be absorbed on antigen-primed H-2-incompatible T cells but cannot suppress H-2-incompatible mice. In addition to this H-2 restriction, which maps to the I-J subregion, monoclonal TsF2 also has an Igh genetic restriction. The present results are combined with previous data to describe the cellular interactions leading to immune suppression.

Absorption↗
PubMed1981

Antigen- and receptor-driven regulatory mechanisms. VIII. Suppression of idiotype-negative, p-azobenzenearsonate-specific T cells results from the interaction of an anti-idiotypic second-order T suppressor cell with a cross-reactive-idiotype-positive, p-azobenzenearsonate-primed T cell target.

The suppressor pathway that regulates the T cell response to p-azobenzenearsonate (ABA)-coupled cells has been studied. It has been found that the ability of anti-idiotypic second-order T suppressor cells (Ts2) to inhibit T cell-dependent delayed-type hypersensitivity (DTH) responses depended upon the presence of cross-reactive-idiotype (CRI)-bearing T cells present in ABA-primed mice. This suppressor T cell subset, termed Ts2, so exists with CRI-negative T cells that mediate DTH in vivo. It appears that antigen-activated CRI+ Ts3 require signals from the anti-CRI Ts2 subset to suppress DTH reactions in an idiotype-nonspecific manner. The relevance of these observations to a comprehensive scheme of T and B cell regulation is discussed.

Animals↗