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Biomedical subjects

B Benacerraf

Publications and source records attributed to B Benacerraf.

At least 145 records · Page 8Linked to original sources
PubMed1981

Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. VIII. Suppressor cell pathways in cutaneous sensitivity responses.

In the current study, we examine the mechanism of suppression of cutaneous sensitivity (CS) responses to 4-hydroxy-3-nitrophenyl acetyl succinimide ester. Intravenous administration of haptenated syngeneic spleen cells induces a state of hapten-specific tolerance involving I-J bearing suppressor T cells that function at either the induction phase or the effector phase of the CS response. The effective phase suppressor cells (Tse) are genetically restricted by both Igh and H-2 region genes. However, a third cell population is also required in he immune lymphocyte population for immune suppression. This third cell population, termed Ts3, is an I-J+, cyclophosphamide-sensitive T cell, as shown by reconstitution experiments. Further, the Tse-Ts3 interaction is restricted by genes in he H-2 and Igh gene complexes. The results are discussed with respect to the pathway of cellular interactions leading to immuno suppression.

Animals↗
PubMed1981

Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. VII. Idiotype-specific suppression of plaque-forming cell responses.

The ability of suppressor cells induced by the intravenous administration of 4-hydro-3-nitrophenyl acetyl (NP)-modified syngeneic cells to reduce an idiotypic B cell response was studied in both an in vivo and an in vitro system. Idiotype-positive B cells were assayed by the ability of guinea pig anti-idiotypic antiserum to specifically inhibit idiotype-positive plaque formation. It was found that up to 57% of the PFC response in vivo and 100% of the PFC response in vitro was inhibitable with antiidiotypic antiserum. The expression of these idiotype-positive B cells could be suppressed by the transfer of spleen cells form mice treated 7 d previously with NP coupled syngeneic cels. T cells are both required and sufficient for the transfer of idiotype specific suppression. The induction of these idiotype-specific T suppressor cells directly with antigen suggests that recognition of unique determinants on cell surfaces is important for regulation of lymphoid cell interactions. The role of idiotype-specific suppressor cells in the network of lymphoid interactions is discussed.

Animals↗
PubMed1981

Mechanisms of regulation of cell-mediated immunity. VII. Suppressor T cells induced by suboptimal doses of antigen plus an I-J-specific allogeneic effect.

Intravenous injection of 0.01 mM 2,4,6-trinitrobenzene sulfonic acid-derivatized syngeneic lymphoid cells generates a Thy-1-positive, antigen-specific suppressor cell for contact sensitivity which requires an I-J allogeneic effect to become fully activated. It is necessary and sufficient for all allogeneic effect to be directed solely against the suppressor cell, and once activated, the cell can suppress in an H-2-unrestricted fashion. The results are discussed in the framework of entry into the suppressor pathway, the allogeneic effect as a reflection of normal physiologic processes, and the importance of I-J as a receptor and signal among cells in the suppressor pathway.

Animals↗
PubMed1981

Antigen- and receptor-driven regulatory mechanisms. VII. H-2-restricted anti-idiotypic suppressor factor from efferent suppressor T cells.

Azobenzenearsonate (ABA)-specific T cell-derived suppressor factor (TsF1) from A/J mice was used to induced second-order suppressor T cells (Ts2). Comparison of suppressor T cells induced by antigen (Ts1) with Ts2 induced by TsF1 revealed that Ts1 were afferent suppressors active only when given at the time of antigen priming, and not thereafter, whereas Ts2 could act when transferred at any time up to 1 d before antigen challenge for a delayed-type hypersensitivity response. This was true even when the recipient could be shown to be fully immune before transfer of Ts2, thus defining these cells as efferent suppressors. The anti-idiotypic specificity of the Ts2 was demonstrated by the ability of Ts to bind to idiotype (cross-reactive idiotype [CRI])-coated Petri dishes. A soluble extract from Ts2 (TsF2) was also capable of mediating efferent suppression that was functionally antigen- (ABA) specific. Comparison of TsF1 with this new factor, TsF2, revealed that both lack Ig-constant-region determinants, possess H-2-coded determinants, and show specific binding (to ABA and to CRI+-Ig, respectively). TsF1 acts in strains that differ with respect to H-2 and background genes, whereas TsF2 shows H-2- and non-H-2-linked genetic restrictions. This existence of H-2 restriction of TsF2 activity suggests that the apparent discrepancies in studies of H-2 restriction of TsF may be a result of the analysis of two separate classes of TsF, only one of which shows genetically restricted activity, thus unifying several models of suppressor cell activity.

Animals↗
PubMed1981

Effect of anti-Lyb3 antiserum on poly (L-glutamic acid, L-lysine)-induced B cell tolerance.

The effect of anti-Lyb3 antiserum on antigen-specific B cell tolerance was investigated. The intraperitoneal injection of the nonimmunogenic copolymer L-glutamic acid60, L-lysine (GL) specifically reduces the ability of murine B cells to form GL-specific plaque-forming cell responses following challenge with the immunogenic conjugate of GL coupled to fowl gamma-globulin. It was found that this tolerance could be reversed or blocked by the intravenous injection of microliter quantities of anti-Lyb3 antiserum. However, this dose of antiserum neither reversed T cell tolerance induced with protein-coupled syngeneic erythrocytes nor induced tolerized B cells to secrete antibody. The results suggest that B lymphocytes can be rescued from GL-induced tolerance soon after induction and that Lyb3 determinants may play a functional role in the activation of antigen-specific B lymphocytes.

Animals↗
PubMed1981

Cellular interactions in the generation of cytolytic T lymphocyte responses. Analysis of the helper T cell pathway.

Murine splenic lymphocytes exhibit a requirement for helper T cells for the induction of a cytolytic T lymphocyte response to suboptimal doses of allogeneic cells, membranes from allogeneic cells, or purified H-2 antigen in liposomes. The conditions where a requirement for help is apparent are the same conditions where a dependence on splenic adherent cells (SAC) has been demonstrated (Weinberger, O. et al., PROC. Natl. Acad, Sci, USA 1980. 77: 6091). Help can be provided in the form of primed, radioresistant, Ly-1+ spleen or lymph node cells or helper factor (interleukin 2, IL-2). A factor generated from phytohemagglutinin-stimulated human lymphocytes, when added to culture in the presence of antigen, bypassed the requirement for Ia+ SAC and helper cells. IL-2 reconstituted the response to H-2K(k) in liposomes in cultures depleted of SAC, strongly suggesting that the helper cell must see antigen re-expressed by an antigen-presenting cell, whereas the prekiller does not. IL-2 could be generated by culturing Ly-1+ murine spleen cells with H-2K(k) pulsed on SAC.

Animals↗
PubMed1981

Suppressor factor from a T cell hybrid inhibits delayed-type hypersensitivity responses to azobenzenearsonate.

By using polyethylene glycol 1540, BW5147 AKR T lymphoma cells were fused with splenocytes from A/J mice treated so as to induce suppressor T cells specific for azobenzenearsonate (ABA). Of 576 microwells originally seeded, 132 demonstrated growing cell clones, 4 of which produced an ABA-binding supernatant factor. When tested in vivo for suppression of delayed-type hypersensitivity to ABA, two of these cell lines, A4 and F12, were shown to produce suppressive supernatant factors. Fluorescence analysis of the F12 cells with appropriate antisera demonstrated this T cell hybrid to be Thy 1.2+, Lyt 1+,2-, and surface immunoglobulin negative, the surface marker phenotype of conventional ABA-specific suppressor T cells. This cloned suppressor cell line, F12, produces a culture supernatant factor that is suppressive at dilutions up to 1:100 and has provided material for genetic and immunochemical analysis.

Animals↗
PubMed1981

Genetic and serological analysis of the expression of crossreactive idiotypic determinants on anti-p-azobenzenarsonate antibodies and p-azobenzenarsonate-specific suppressor T cell factors.

Data are reported on the genetic control and structure of antigen-specific suppressive molecules obtained from azobenzenearsonate (ABA)-specific suppressor T cells (Ts). Ts-derived suppressor factors (TsFs) were previously shown to bear determinants encoded by genes of the I-J subregion of the H-3 major histocompatibility complex and structures encoded by VH (variable region of heavy chains) genes linked to the Igh locus. To further characterize TsF we have made use of a K light (L) chain variable region (VK) genetic marker linked to the locus governing expression of a crossreactive idiotype on anti-ABA antibodies. The experiments evaluated the possible contribution to TsF of structures under control of the VK locus. TsF was prepared in strains of mice with known Igh and VK genes. Mice carrying Igh-1e genes produced TsF that was retained by an immunoadsorbent containing bound anti-idiotype antibodies; the genetic constitution at the VK locus was not relevant. By using a panel of anti-idiotypic antibodies prepared against the antigen-binding site of antibody carrying the idiotype, against determinants outside the site or against VH structures, we determined that idiotypic structures on the TsF are associated with V-region elements associated with the H chain and not with the binding site formed by a VH-BL combination.

Animals↗
PubMed1981

Antigen-presenting cell function in induction of helper T cells for cytotoxic T-lymphocyte responses: evidence for antigen processing.

We demonstrate that splenic adherent cells (SACs) play an active role in the presentation of H-2Kk antigen for an alloreactive cytotoxic T-lymphocyte (CTL) response. If antigen is incubated with SACs for 12 hr, they will provide maximal stimulation and present the antigen in the context of their Ia molecules. UV irradiation of these SACs, prior to the 12-hr incubation with H-2Kk antigen, abrogates this stimulatory capacity. Macrophage-bound antigen is not sufficient for stimulation of a response; a second signal is required as well, that, in our system, is provided by phorbol myristic acetate. The SACs are involved in the activation of helper T cells; however, they are not required for presentation of antigen to the precytotoxic T-lymphocyte, which requires two signals for activation, one provided by antigen and the other by a T-cell-derived helper factor.

Animals↗
PubMed1981

B-lymphocyte responses to trinitrophenyl-conjugated Ficoll: requirement for T lymphocytes and Ia-bearing adherent cells.

These studies were done to characterize the cellular requirements for B-lymphocyte responses to the haptenated polysaccharide trinitrophenyl-conjugated Ficoll. By using an in vitro microculture system, it was demonstrated that hapten-specific anti-trinitrophenyl-conjugated Ficoll plaque-forming cell responses by B lymphocytes require Ia-bearing adherent accessory cells and Thy 1+ Lyt 1+2- nylon wool-nonadherent (T) lymphocytes. Such T cells could be primed in vivo with nonderivatized Ficoll to show carrier-specific helper cell function for derivatized Ficoll responses in vitro. The implications of these findings for our understanding of b-lymphocyte triggering by so-called T-independent antigens are discussed.

Animals↗
PubMed1981

Impairment of antigen-presenting cell function by ultraviolet radiation. II. Effect of in vitro ultraviolet irradiation on antigen-presenting cells.

The s.c. injection of 10 mM 2,4,6-trinitrobenzene sulfonic acid (TNBS) derivatized splenic adherent cells (SACs) into syngeneic mice primes for contact sensitivity or delayed-type hypersensitivity (DTH) when these animals are challenged with picryl chloride on the ear or trinitrophenol (TNP)-coupled cells in the footpad, respectively. If recipient mice are exposed to ultraviolet light (UV) irradiation and are immunized with normal TNP-treated SACs, they develop marked DTH reaction upon challenge but develop limited DTH reactions if immunized with hapten-derivatized SACs that had been obtained from UV-treated recipients. Moreover, if the SACs are obtained from normal mice but are treated in vitro with UV light (1.2 to 1.4 mJ/cm2/sec over the wavelength range 280 to 340 nm at a tube to target distance of 20 cm) these cells can neither prime nor elicit hapten-specific T cell immunity in UV-treated recipients. If UV-treated TNP SACs are used to prime UV-irradiated recipients, TNP-specific suppressor T cells are generated rather than T effector cells.

Animals↗
PubMed1981

Idiotypic analysis of anti-GAT antibodies. VIII. Comparison of interstrain and allotype-associated idiotypic specificities.

A guinea pig anti-idiotypic antiserum made against pooled specifically purified A/J anti-GAT antibodies was characterized. This antiserum contains anti-idiotypic antibodies specific to interspecies, interstrain, and allotype-linked idiotypic determinants. These idiotypic determinants are associated with the combining sites of idiotypic antibodies that are induced by GT-related but not GA-related antigenic moieties. Genetic and strain distribution studies indicated that the shared allotype-linked idiotypic determinants are controlled by Igh-1e- or Igh-1b-linked genes. The interrelationships of the allotype-linked and interstrain CGAT idiotypic specificities are described using monoclonal anti-GAT hybridoma antibodies. Four of 7 hybridoma anti-GAT antibodies of C57BL/6 origin expressed a major fraction of the idiotypic specificities of A/J anti-GAT antibodies. These 4 hybridoma antibodies also carried the common interstrain idiotype, termed CGAT, but not all CGAT-bearing anti-GAT hybridoma antibodies expressed the allotype-linked idiotypic specificities. The Ig-1b-positive, F17-167.1 hybridoma anti-GAT antibody was used as a ligand to selectively identify the major allotype-linked idiotypic specificities, which were designated Gte idiotype.

Animals↗
PubMed1981

Analysis of Ir gene function using monoclonal antibodies: independent regulation of GAT and GLPhe T cell responses by I-A and I-E subregion products on a single accessory cell population.

T cell proliferative responses to the synthetic polypeptides GAT and GLPhe are under Ir gene control. GAT responses are regulated by gene(s) in the I-A subregion, and GLPhe responses are controlled by a pair of complementing genes mapping to the I-A and I-E subregions. We demonstrate that monoclonal antibody to the I-A gene product inhibits GAT proliferation but not the GLPhe response, whereas a monoclonal antibody to the I-E associated Ia-7 determinant inhibits GLPhe but not GAT proliferation, which indicates independent involvement of each Ia determinant in antigen presentation for the T cell response to these antigens. Use of the same subregion-specific monoclonal antibodies in complement-dependent lysis demonstrates that the antigen-presenting cells for GAT and GLPhe express both I-A and I-E products. The possibility that an Ia subregion-specific "self-receptor" functions on the reactive T cells as a regulatory element is discussed.

Allergy and Immunology↗
PubMed1981

Acquisition of syngeneic I-A determinants by T cells proliferating in response to poly (Glu60Ala30Tyr10).

The T cell proliferative response in mice to the synthetic polymer GAT is under Ir gene control, mapping to the I-A subregion of the H-2 major histocompatibility complex (MHC). Antigen-dependent proliferation in vitro of in vivo GAT-primed lymph node cells can be inhibited by a monoclonal antibody to Ia-17, an I-A public determinant. Using this antibody for direct immunofluorescent analysis, T cells in GAT-stimulated proliferative culture are identified that express syngeneic I-A during culture. This expression is strictly antigen dependent, requires restimulation in vitro, and requires the presence of I-A-positive adherent antigen-presenting cells. T cells bearing I-A can be enriched by a simple affinity procedure, and I-A-positive cells separated on a FACS are shown to retain antigen-specific reactivity. The acquisition of I-A determinants by T cells under these culture conditions is not nonspecific. The Ia determinants borne by T cell blasts appear to be dictated by the I subregion to which the relevant Ir gene maps, and which codes for the Ia molecule involved in presentation of the antigen. Thus, (B6A)F1 (H-2b X H-2a)F1 LNC express I-Ak antigens when proliferating to GAT but not when stimulated by GLPhe, the response to which is under I-E subregion control. The relation of Ir gene function to Ia-restricted antigen presentation and self-Ia recognition is discussed.

Animals↗
PubMed1981

Ir gene control of the cytotoxic T lymphocyte response to Sendai virus: H-2k mice are low responders to Sendai.

H-2k mice generate a secondary in vitro cytotoxic T lymphocyte response to Sendai virus 20- to 100-fold weaker than those of other haplotypes tested (H-2b,d,q,s). This immune response defect maps to both H-2K and H-2D. H-2k x H-2d F1 mice (responder x nonresponder) only lyse targets that have the d allele at H-2K and/or H-2D. H-2k targets are equally lysable with anti-Sendai antibody. Furthermore, H-2k mice demonstrate normal antibody and T cell proliferation responses to Sendai virus. The Ir gene defect therefore appears to be limited to the generation of the cytotoxic T lymphocytes.

Animals↗
PubMed1981

Plaque-forming cell responses to trinitrophenyl (TNP)-L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) in microcultures are not under conventional Ir gene control.

The IgM plaque-forming cell response to trinitrophenyl (TNP)-conjugated L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) was studied in an in vitro microculture system. Contrary to expectations, this response was not found to be under conventional H-2 linked Ir gene control. Thus, both classical responder BALB/c (H-2d) and non-responder DBA/1 (H-2q) spleen cells gave equivalent anti-TNP PFC responses to TNP-GAT in these cultures. Experiments were performed to determined if haptenation had changed the GAT carrier so as to remove it from GAT-specific Ir gene control. It could be demonstrated that TNP-GAT elicited in vivo anti-GAT PFC responses showing typical Ir control in the BALB/c and DBA/1 strains; that anti-hapten and anti-carrier PFC responses to DNP-GAT in vivo were similarly controlled; and that the TNP-GAT compound remained a T cell- and Ia+ accessory cell-dependent antigen in vitro. Furthermore, the microculture system allowed GAT-specific T helper cells to be detected in the spleens of DBA/1 mice treated with GAT in vivo under conditions eliciting a predominant suppressor T cell response under usual conditions of assay. These findings contrast with the Ir gene regulation of TNP-(T,G)-A--L responses seen under identical culture conditions. The implications of these results for our understanding of the site of Ir gene action and the target of suppression in the GAT model are discussed.

Animals↗