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Biomedical subjects

B Benacerraf

Publications and source records attributed to B Benacerraf.

At least 163 records · Page 9Linked to original sources
PubMed1981

The role of T cell sets in the rejection of a methylcholanthrene-induced sarcoma (S1509a) in syngeneic mice.

The ability of different T cell sets to confer protection in mice against a methylcholanthrene-induced sarcoma, S1509a, was examined. Intravenous infusion of lymph node and spleen cells from A/J donors immunized with S1509a into normal A/J recipients retarded subcutaneous growth of S1509a but did not lead to complete eradication of the tumor during a 9-day period of observation. This protective effect was lost if the transferred cells were treated with anti-Thy 1.2 and complement. The ability of different populations of lymphoid cells to retard tumor growth after inoculation with tumor cells subcutaneously was examined (Winn assay). Nylon-wool-passed cells from lymph nodes and spleens of tumor immunized animals were treated either with anti-Ly 1.2 or with anti-Ly 2.2 antiserums and complement and inoculated with tumor cells in normal A/J mice. The tumor was measured daily for 10 or more days. Ly l cells and unfractionated T cells efficiently suppressed tumor growth; Ly 23 cells had little or no effect. When small numbers of Ly 1 cells were injected along with twice as many Ly 23 cells, the growth of the tumor was also inhibited. Histologic examination of inoculated sites at 24-72 hours after local transfer showed a more intense mononuclear infiltrate in animals inoculated with tumor cells and T cells from immunized animals than in animals given injection with tumor cells alone, or with tumor cells and T cells from nonimmunized animals. The findings indicate that Ly 1 cells are capable of retarding the growth of the sarcoma, presumably by eliciting a delayed hypersensitivity reaction. By contrast, Ly 23 cells, which can mediate cytotoxicity, had little or no effect on tumor growth.

Animals↗
PubMed1980

Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. VI. Evidence for different T cell receptors in cells that mediate H-21-restricted and H-2D-restricted cutaneous sensitivity responses.

We have previously shown that cross-reactive sensitivity (CS) responses induced by 4-hydroxy-3-nitrophenyl acetyl-O-succinimide (NP-O-Su) and elicited by its 5-iodo analogue, 4-hydroxy-5-iodo-3-nitrophenyl acetyl-O-succinimide were observed in strains of mice possessing the Igh-1b allotype, but not in strains bearing allotypes Igh-1c or Igh-1j. These CS responses are mediated by T cells and can be transferred to naive recipients that are homologous at either the H-2K, H-2I, or H-2D regions of the major histocompatibility complex. We now extend our analysis of cross-reactive 4-hydroxy-3-nitrophenyl-acetyl (NP)-induced CS responses to inbred strains of mice expressing additional Igh-1 allotypes. In contrast to NP-induced delayed-type hypersensitivity responses, which only display 4-hydroxy-5-iodo-3-nitrophenyl acetyl (NIP) cross-reactivity in Igh-1b-bearing mice, cross-reactive CS responses can also be elicited in NP-primed mice carrying the Igh-1d, Igh-1e, or Igh-1f allotypes. Moreover, cross-reactive NP-induced CS responses could be transferred by NP-O-Su-primed lymph node cells from the AKR (Igh-1d) strain, into naive recipients homologous at the H-2D region, but only non-cross-reactive NP responses could be transferred into strains homologous at the H-2I region. Furthermore, the lack of cross-reactivity in the Igh-1j-bearing C3H strain was not the result of an inability of these mice to recognize NP in association with H-2K/D products, because NP-O-Su-primed cells from C3H donors transferred NP-specific CS responses into both H-2D and H02I homologous recipients. The results are discussed with respect to the nature of the T cell receptors that control NP responses.

Animals↗
PubMed1980

Antigen- and receptor-driven regulatory mechanisms. V. The failure of idiotype-coupled spleen cells to induce unresponsiveness in animals lacking the appropriate VH genes is caused by the lack of idiotype-matched targets.

A/J anti-p-azobenzenearsonate (ABA) antibodies bearing cross-reactive idiotypic (CRI) determinants, when coupled to spleen cells and then injected intravenously into naive animals, stimulate suppressor T cell (Ts) responses. Moreover, previous studies have demonstrated that the ability of such idiotype-coupled spleen cells to induce immune unresponsiveness to subsequent immunization with ABA-coupled spleen cells is linked to Igh-1 genes. Thus, CRI bearing antibodies from A/J mice, when conjugated to normal BALB/c spleen cells in vitro and then injected intravenously to syngeneic BALB/c mice, failed to induce tolerance in these animals. However, spleen cells taken from these animals transferred significant degrees of suppression to Igh-1 congenic C.AL-20 but not to H-2 congenic, Igh-1 distinct B10.D2 mice. Therefore, the failure of CRI-coupled spleen cells to induce suppressor cell- mediated unresponsiveness in animals unable to express the appropriate VH genes (i.e. BALB/c and B10.D2) appears to be caused by the lack of idiotype- matched targets. The notion that the ability to express certain Vn genes in the recipient animal is a prerequisite for suppressor cell function was further supported by the observation that suppressor cells induced in C.AL-20 mice failed to transfer any degree of suppression to BALB/c mice. The ability to transfer suppression from BALB/c mice to C.AL-20 mice is a T cell- dependent phenomenon, since in vitro treatment with anti-Thy 1.2 antiserum and complement completely abrogated suppressor cell function. Furthermore, these suppressor T cells are antigen specific and can be enriched on idiotype-coated petri dishes, indicating they possess anti-idiotypic receptors. Therefore, appropriate anti-idiotype and idiotype interaction is essential for the manifestation of suppressor T cell function in ABA-specific suppressor pathways.

Animals↗
PubMed1980

Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. V. Role of idiotypes in the suppressor pathway.

4-Hydroxy-3-nitrophenyl (NP) derivatized syngeneic spleen cells injected intravenously stimulate maturation of an antigen-binding, idiotype-bearing induction-phase suppressor cell population, as well as an idiotype-binding anti-idiotype-bearing effector-phase suppressor cell population. Both cell types are present simultaneously in the spleen cell population 7-d after their induction. Furthermore, the cell population with antigen-binding properties can, in the presence of NP-derivatized syngeneic cells, induce a population of effector suppressor cells. The precursors of the effector suppressor population are not sensitive to concentrations of cyclophosphamide which prevented the generation of induction phase suppressor cells. These data provide direct evidence in support of the theory of network regulation of immune suppression. X

Animals↗
PubMed1980

Genetic control of a shared idiotype among antibodies directed to distinct specificities.

We developed an idiotypic radioimmunoassay system that detects shared idiotypic determinants, termed GTGL idiotype, on antibodies bearing distinct antigen-binding specificities in various mouse strains. Either poly-(Glu, Tyr) (GT)- or poly-(Glu, Lys) (GL)-related determinants are able to induce anti-GT and anti-GL (GTGL)-idiotypic antibodies. Strain distribution studies indicate that GTGL-idiotypic antibodies are readily induced and frequently expressed in antisera obtained from 25 different mouse strains immunized either with GT-related or GL-related polymers. The ability to express GTGL-idiotypic antibodies is a dominant trait and is controlled by Igh-linked gene(s). In addition, we demonstrated that in anticopolymer of L-glutamine acid60- L-alanine30-L-tyrosine (GAT) and anticopolymer of L-glutamic acid54-L-lysine35-L-phenylalanine11(GLphi) antisera, both antibodies uniquely specific to GAT or GLphi, respectively, and antibodies bearing dual specificities for GAT and GLphi, expressed GTGL idiotype. The genetic implications of these findings are discussed. X

Alanine↗
PubMed1980

Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. III. Interaction of effector suppressor T cells is restricted by H-2 and Igh-V genes.

4-Hydroxy-3-nitrophenyl acetyl (NP)-derivatized syngeneic spleen cells administered intravenously induced a population of suppressor T cells that could suppress mice previously primed to NP. The effect was demonstrable when the suppressor cells were transferred to NP-primed mice on the day of challenge for delayed-type hypersensitivity (DTH) responses. In contrast to the suppressor T cell population, which abrogates 5-iodo derivative of NP (NIP)-specific DTH responses when administered before antigen priming, the effector-phase suppressors did not efficiently suppress NIP-specific DTH responses, and were not lysed by treatment with antiidiotype plus complement. Adoptive transfer experiments between major histocompatibility complex and allotype congenic strains of mice allowed demonstration of both Igh-V and I-A restrictions in the transfer of this cell population. The implications of these data in terms of network theories and proposed cellular models for negative immunoregulation were discussed.

Animals↗
PubMed1980

Antigen- and receptor-driven regulatory mechanisms. IV. Idiotype-bearing I-J+ suppressor T cell factors induce second-order suppressor T cells which express anti-idiotypic receptors.

Administration of azobenzenearsonate (ABA)-coupled syngeneic spleen cells intravenously to A/J mice leads to the generation of suppressor T cells (Ts1) which exhibit specific binding to ABA-bovine serum albumin (BSA)-coated dishes. These Ts1 share idiotypic determinants with the major cross-reactive idiotype (CRI) of the anti-ABA antibodies of A/J mice, and also produce a soluble suppressor factor (TsF) bearing CRI and I-J subregion-coded determinants. Injection of this TsF into naive A/J mice elicits a second set of specific suppressor cells (Ts2) which are not lysed by anti-CRI antibody plus C, and which do not bind to ABA-BSA-coated dishes. However, in contrast with Ts1, these Ts2 do bind to plates bearing CRI+ anti-ABA immunoglobulin. Thus, Ts2 exhibit anti-idiotypic specificity. These data indicate that antigen elicits the production of a soluble T cell product bearing both variable portion of the Ig heavy chain (VH) and I-J subregion-coded determinants which serves to communicate between T cell subsets to establish an idiotype-anti-idiotype regulatory pathway.

Animals↗
PubMed1980

Antigen-specific T cell-mediated suppression. V. H-2-linked genetic control of distinct antigen-specific defects in the production and activity of L-glutamic acid50-L-tyrosine50 suppressor factor.

The occurrence of distinct genetic defects affecting the generation of T cell-derived suppressor factor (TsF) or the suppressive activity of such TsF was investigated. For the synthetic polypeptide L-glutamic acid50-L-tyrosine50 (GT), it could be shown that the nonsuppressor strain A/J fails to produce suppressor T cells (Ts1) capable of GT-TsF generation upon challenge with GT. Conversely, B6, another nonsuppressor strain, produces GT-TsF active on other allogeneic strains such as A/J, but itself fails to be suppressed by this material. (B6A)F1 mice both make GT-TsF, and are suppressed by it. Further experiments revealed that the production of GT-TsF and the ability to be suppressed by GT-TsF are under the control of H-2-linked genes. Finally, the defect in GT-TsF activity in B6 mice was shown to be exquisitely antigen specific, in that this strain can be suppressed by a closely related TsF specific for L-glutamic acid60-L-alanine30-L-tyrosine10. It is suggested that H-2 (I) control of suppressor T cell (Ts) activity may reflect the involvement of I-A and I-C gene products in antigen presentation to Ts in analog with other T cell subsets, and that TsF function might also involve such presentation, in this case of the idiotypic structures of the TsF-combining site. Predictions deriving from this hypothesis are discussed, including the possibility that H-2 linked immune response genes regulate auto-anti-idiotypic responses in immune networks.

Animals↗
PubMed1980

Antigen- and receptor-driven regulatory mechanisms. III. Induction of delayed type hypersensitivity to azobenzenearsonate with anti-cross-reactive idiotypic antibodies.

Delayed-type hypersensitivity (DTH) to p-azobenzenearsonate (ABA) can be induced in A/J mice with intravenous injection of minute amounts of anti-cross-reactive idiotypic (CRI) antibodies, providing that the animals have been pretreated 2 d earlier with low doses of cyclophosphamide (50 mg/kg). However intravenous injection of the F(ab')2 fragments of the anti-CRI antibodies or subcutaneous administration with anti-CRI antibodies induces comparable immunity in both cyclophosphamide-pretreated and normal nontreated animals. Furthermore adoptive transfer experiments indicate that lymph node cells taken from animals sensitized with anti-CRI 4 d earlier can adoptively transfer immunity to naive recipients. Transfer of immunity is mediated by a population of thymus-dependent (T) cells, which express idiotypic structures on their surface. Treatment of effector cells with either anti-theta serum or anti-idiotypic antibodies plus complement completely abrogated their ability to transfer immunity. In addition idiotype-bearing suppressor T cells induced with ABA-coupled spleen cells inhibit the development of ABA-specific DTH induced with anti-CRI antibodies. Genetic analysis revealed that the ability of anti-CRI antibodies to induce ABA-specific DTH was linked to Igh-1 heavy-chain allotype. Anti-idiotypic antibodies to the major CRI associated with anti-ABA antibodies in A/J mice failed to induce significant immunity in BALB/c mice (H-2d, Igh-1a). Nevertheless, they were able to induce significant immunity in C.AL20 mice (H-2d, Igh-1d) which possess a heavy-chain allotype similar to that of A/J mice.

Animals↗
PubMed1980

Feedback suppression of the immune response in vitro. I. Activity of antigen-stimulated B cells.

Feedback regulation of the primary humoral immune response to sheep erythrocytes (SRBC) was studied in vitro. Whole spleen cells or spleen cell subpopulations were incubated with antigen for 4 d under Mishell-Dutton conditions (education) and the surviving cells tested for regulatory activity in fresh anti-SRBC spleen cell cultures assayed by measuring plaque-forming cells on day 4. The data indicate that (a) whole spleen cells educated with SRBC exert potent antigen-specific suppression in the assay culture, (b) surface Ig- (sIg-) cells (T cells) prepared by either nylon-wool separation or fractionation on rabbit anti-mouse-Ig-coated polystyrene Petri dishes failed to generate suppressive activity when educated alone, in 2-mercaptoethanol, or in the presence of additional macrophages, (c) surface Ig (sIg+) (B) cells educated alone also failed to generate suppressor cells, and (d) mixing sIg- (T) and sIg+, Lyt 123- (B) cells reconstituted the ability to induce suppressor cells under these conditions. The antigen-primed cell actually required to transfer suppression was also characterized by separating cells using anti-Ig coated dishes, by fluorescence-activated cell sorting and by anti-Lyt treatment. All these methods clearly identified sIg+ (B) and not sIg+ (T) cells as the important educated cells. It is concluded that under our conditions, T cell-dependent B cells triggered by antigen during primary in vitro cultures cause potent specific feedback suppression of humoral responses. Possible mechanisms for this suppression, including antigen blockade or anti-idiotypic responses, are discussed.

Animals↗
PubMed1980

Feedback suppression of the immune response in vitro. II. IgVH-restricted antibody-dependent suppression.

Feedback suppression of the primary humoral immune response to sheep erythrocytes (SRBC) in vitro was induced with cell-free supernate material derived from antigen-(SRBC) activated B (sIg+) cells. This soluble products bears Ig determinants and binds to the eliciting antigen (SRBC). The activity of this antibody in suppressing anti-SRBC plaque-forming cell responses is restricted to spleen cell cultures containing B cells sharing VH genes with the B cells producing the suppressive antibody. The anti-hapten (trinitrophenyl) response to derivatized SRBC is not affected by antigen-primed B cells or their products. These data are compatible with suppression being mediated by anti-antigen antibody, either (a) via blockade of different SRBC epitopes recognized by a limited set of B cell clones in each mouse strain, (b) via triggering of an anti-idiotypic response, either antibody or suppressor T cell in nature, restricted to activity in cultures containing B cells sharing VH structures with the original antibody, or (c) via interference by preformed antibody with T cell help directed at idiotype bearing B cells.

Animals↗
PubMed1980

The characterization of the delayed-type hypersensitivity reaction to H-Y antigens.

We have evaluated the ability of certain inbred strains of mice to develop a delayed-type hypersensitivity response to the male H-Y antigen. It was found that C57BL/10, B10.GD and B10.A(5R) female mice responded to syngeneic male cells. B10.A(4R) females also responded to B10.A(4R) male cells although the reactivity was somewhat slighter. B10.A(2R), B10.D2 and BALB/c female mice could not respond to immunization with syngeneic male cells. The response was male-antigen specific and transferable by thymus-derived cells. Moreover, suggestive evidence of representation of H-Y was obtained, based on the ability of responder strains immunized with syngeneic cells to react to nonresponder male cells upon challenge.

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