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Biomedical subjects

M S Sy

Publications and source records attributed to M S Sy.

At least 109 records · Page 6Linked to original sources
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

Antigen-specific suppression of cytotoxic T cell responses: an idiotype-bearing factor regulates the cytotoxic T cell response to azobenzenearsonate-coupled cells.

When A/J mice are injected subcutaneously with azobenzenearsonate- (ABA) coupled spleen cells, their splenocytes contain primed ABA-specific cytotoxic T lymphocyte (CTL) precursors. Animals that are not primed in vivo do not develop vigorous CTL activity when assessed after in vitro culture with ABA-coupled stimulators. Suppressor molecules derived from ligand-induced first-order ABA-specific suppressor T cells were evaluated for their ability to limit cytolytic T cell development. We have shown that an idiotype-bearing, hapten-specific suppressor factor suppresses priming for CTL in an H-2-unrestricted but allotype-restricted manner. The implication of these studies to regulatory networks is discussed.

Animals↗
PubMed1982

Antigen receptors on murine T lymphocytes in contact sensitivity. II. Presentation and characterization of syngeneic anti-idiotype serum against DNFB-sensitized T cells.

This manuscript describes the preparation and characterization of a syngeneic antiserum raised in BALB/c mice against nylon wool-purified lymph node (LN) T cells from 2,4-dinitrofluorobenzene- (DNFB) sensitized BALB/c mice. This antiserum (anti-T DH-DNP) plus complement blocks the ability of LN or purified T cells from DNFB-sensitized donors to transfer immunity to naive recipients. The inhibitory activity of the serum is due to antibodies; these antibodies have specificity for idiotype (Id) determinants as shown by their ability to bind to purified mouse anti-DNP antibodies but not to rabbit anti-DNP or normal mouse Ig. Inhibition of transfer of immunity by the anti-Id serum is not restricted by either H-2 gene products or Igh-1 allotypes. The antiserum is antigen specific when tested on LN cells from oxazolone-sensitized mice, but has a low level of cross-reactivity against T cells from 2,4,6-trinitrochlorobenzene- (TNCB) sensitized mice. In addition, it was shown that naturally occurring anti-Id antibodies, epsilon-DNP-L-lysine, or DNP-protein (but not NIP-protein) and the anti-Id in syngeneic anti-T DH-DNP serum compete for similar binding sites on DNFB-immune T cells. We interpret these findings to indicate that immunization of mice with T cells from DNFB-sensitized syngeneic mice induces the production of anti-Id antibodies. These anti-Id antibodies are specific for determinants expressed on the T cell receptor or receptor subsite that is specific for the hapten DNP.

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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↗
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↗
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

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

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

Ligand-receptor relationships in immune regulation.

The relationship between ligand, idiotype-bearing ligand-binding T suppressor cells (Ts), and antiidiotypic Ts is discussed. The suppressor pathway involves the activation by ligand of first-order idiotypic Ts (Ts1) which elaborate idiotype-bearing T suppressor factors (TsF). TsF readily induced second-order antiidiotypic TS2 cells. The genetic restrictions imposed on the immune system once perturbed by antigen are evaluated.

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

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- 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.

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