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M S Sy

Publications and source records attributed to M S Sy.

At least 127 records · Page 7Linked to original sources
PubMed1980

Mechanisms of regulation of cell-mediated immunity. VI. Antigen density dependence of the induction of genetically restricted suppressor cells.

We have investigated the relationship of antigen density on cell surfaces to the induction of genetically restricted suppressor T cells (Ts). It was found that Ts able to suppress the development of hapten-specific contact sensitivity were induced by the i.v. inoculation of trinitrobenzene sulfonate (TNBS) hapten-coupled cells. The Ts induced by this technique were found to be gentically unrestricted in terms of generation or expression when 10 mM TNBS were used to prepare the hapten-coupled cells. Transferable suppression could be obtained by 10 mM coupled allogeneic cells or, alternatively, TNP-coupled Ia- syngeneic erythrocytes or even H-2-negative syngeneic tumor cells. However, 1 mM TNBS-derivatized hapten-coupled cells induced Ts that were able to suppress only recipients syngeneic with the tolerogen. The significance of these findings to our understanding of the induction and expression of Ts and the triggering signals that are necessary for their activation are discussed.

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PubMed1980

Nature of hapten-modified determinants involved in induction of T cell tolerance and suppressor T cells to NDFB contact sensitivity.

Unresponsiveness to DNFB contact sensitivity induced by DNP-modified lymphoid cells (DNP-LC) is mediated by two separable pathways: a rapidly induced, long lasting inhibition of reactive T cell clones (donor tolerance), and a transient period of suppressor T cell (Ts) activity. The present report has examined the nature of the hapten-modified determinants responsible for the induction of these pathways by utilizing soluble DNP-LC cell lysate preparations as tolerogens. The results indicate that both DNP-modified MHC and non-MHC encoded determinants can mediate donor tolerance 7 days after tolerization. On the other hand, the induction of Ts requires DNP-modified MHC determinants, since DNP-LC lysates passed over lentil lectin or specific anti-H-2 immunoabsorbent columns lost their ability to induce Ts. Additional experiments showed that the injection of DNP-LC lysate compatible with the recipient strain at the H-2K and H-2D region of the MHC was sufficient for the induction of Ts. We propose that Ts induction involves the direct presentation of DNP-H-2 determinants to Ts precursors, whereas the induction of donor tolerance may involve host processing and presentation of DNP-modified membrane determinants in conjunction with host MHC structures.

Animals↗
PubMed1980

Antigen and receptor-driven regulatory mechanisms. VI. Demonstration of cross-reactive idiotypic determinants on azobenzenearsonate-specific antigen-binding suppressor T cells producing soluble suppressor factor(s).

The first detectable suppressor T cell (Ts) arising after i.v. administration of azobenzenearsonate- (ABA) conjugated syngeneic spleen cells to A/J mice has been studied for its receptor specificity and ability to produce soluble suppressor factor(s). This cell, termed Ts1, has a specific receptor for the eliciting antigen ABA, as demonstrated by selective binding to ABA protein- but not TNP protein-coated plastic dishes. The activity of ABA-Ts1 can be abrogated by treatment with anti-idiotypic antibodies made against anti-ABA antibodies of A/J mice (anti-CRI), indicating that these ABA-binding cells possess a surface receptor structure sharing idiotypic determinants with antibodies of the same specificity. Finally, soluble extracts from, antigen-adherent ABA-Ts1, but not nonadherent cells from the same spleen cell population, possess suppressive activity when assayed directly for afferent suppression or tested for their ability to trigger a second population of Ts (Ts2) in naive recipients. These findings demonstrate a close concordance between a T cell surface receptor, soluble T suppressor factors, and B cell derived antibody, all capable of direct recognition of the eliciting ABA antigen.

Animals↗
PubMed1979

Antigen- and receptor-driven regulatory mechanisms. I. Induction of suppressor T cells with anti-idiotypic antibodies.

Delayed-type hypersensitivity (DTH) to the azobenzenearsonate (ABA) hapten can be readily induced in A/J mice injecting ABA-coupled syngeneic spleen cells subcutaneously. To further characterize this T-cell-dependent immunological phenomenon, the effect of passively administered anti-cross-reactive idiotype common to anti-ABA antibodies of A/J mice (CRI) antibodies on the development of ABA-specific DTH was investigated. Animals given daily injections (of minute amounts) of anti-CRI antibodies subsequent to immunization with ABA-coupled cells show significant reduction of ABA specific responses. This inhibition is antigen specific and requires the intact immunoglobulin molecule, as F(ab')2 treatments were ineffective in suppressing the reaction. Investigations of the mechanism of the anti-CRI-induced suppression of ABA DTH revealed that the observed suppression is a result of the activation of suppressor cells. Spleen cells taken from animals which received anti-CRI antibodies were able to adoptively transfer suppression to naive recipients. This suppression was shown to be mediated by T cells, as anti-Thy1.2 plus complement completely abrogated the transfer of suppression. In addition, animals pretreated with low doses of cyclophosphamide were not suppressed by the administration of anti-CRI antibodies. The genetic restriction of anti-CRI-induced suppression was demonstrated. Antibodies to the major cross-reactive idiotype, (CRI) associated with anti-ABA antibodies in A/J mice were unable to suppress the development of DTH to ABA in BALB/c mice (H-2d, Igh-1a). Such antibodies were, however, fully active in suppressing ABA DTH in the allotype-congenic C.AL-20 strain which has an allotype (Igh-1d) similar to that of A/J (Igh-1e) on a BALB/c background, and which produces humoral antibodies with the CRI.

Animals↗
PubMed1979

Antigen- and receptor-driven regulatory mechanisms. II. Induction of suppressor T cells with idiotype-coupled syngeneic spleen cells.

Anti-p-azobenzenearsonate (ABA) antibodies, coupled covalently to normal syngeneic spleen cells and then given intravenously to normal animals, were found to be potent tolerogens for delayed-type hypersensitivity (DTH) to ABA. The ability of the antibody-coupled cells to induce tolerance was determined to be a result of the cross-reactive idiotype (CRI+) fraction of the antibodies, because anti-ABA antibodies lacking the CRI+ components when coupled to spleen cells were unable to cause any significant inhibition. Furthermore, genetic analysis revealed that the ability of CRI-coupled cells to inhibit ABA-specific DTH is linked to Igh-1 heavy chain allotype, in as much animals which possess heavy chain allotypes similar to that of A/J were sensitive to this inhibition. Adoptive transfer experiments provided evidence that CRI-coupled cells induce suppressor cells, and spleen cells or thymocytes from animals received CRI-coupled cells were able to transfer suppression to naive recipients. In addition, treatment with anti-Thy1.2 serum plus complement completely abrogated their ability to transfer suppression. Thus, this active suppression is a T-cell-dependent phenomenon. In investigating the specificity of these suppressor T cells, it was found that they functioned in an antigen-specific manner and were unable to suppress the development of DTH to an unrelated hapten 2,4-dinitro-1-fluorobenzene.

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PubMed1979

Active suppression of 1-fluoro-2,4-dinitrobenzene-immune T cells. Requirement of an auxiliary T cell induced by antigen.

We investigated T-T cell interactions in the suppression of contact sensitivity. Suppressor cells that block the efferent limb of sensitivity (Ts-eff) can inhibit the passive transfer of contact sensitivity mediated by 1-fluoro-2,4-dinitrobenzene immune cells (T DH). But, Ts-eff cannot block the passive transfer of TDH which comes from cyclophosphamide (Cy) pretreated sensitized mice. We interpret these results to indicate that lymph node cells from sensitized mice contain not only TDH but also another intermediate cell which is required for the suppression of TDH by Ts-eff. This intermediate cell is sensitive to cyclophosphamide and requires antigen activation for its development. It is sensitive to adult thymectomy and anti-brain associated theta serum and is therefore designated as an auxiliary T-suppressor cell (Ts-aux). It is not sensitive to splenectomy and it carries I-J determinants. Ts-aux are required for the activity of suppressors of the efferent limb (Ts-eff) but not of suppressors of the afferent limb (Ts-aff). Thus, in the feedback loops in contact sensitivity, the generation of Tdh is coordinated with the development of auxiliary Ts which are essential for the suppression of those TDH.

Animals↗
PubMed1979

Impairment of antigen-presenting cell function by ultraviolet radiation.

UV light irradiation of BALB/c mice was found to result in impairment of antigen-presenting cell function. Adherent trinitrophenyl-derivatized cells from the peritoneal exudate cell population or the spleen of UV-treated donors could not induce hapten-specific delayed hypersensitivity responses in UV-irradiated syngeneic mice, whereas adherent trinitrophenyl-derivatized cells from normal mice were able to do so. The failure to induce immunity in UV-treated mice by utilizing UV-treated adherent antigen-presenting cells was associated with the development of antigen-specific suppressor T cells. The implication of these results for UV-induced carcinogenesis is discussed.

Animals↗
PubMed1978

Genetic restrictions for the induction of suppressor T cells by hapten-modified lymphoid cells in tolerance to 1-fluoro-2,4-dinitrobenzene contact sensitivity. Role of the H-2D region of the major histocompatibility complex.

Genetic restrictions governing the induction and expression of suppressor T cells (Ts) in tolerance to 1-fluoro-2,4-dinitrogenzene (DNFB) contract sensitivity were studied. Tolerance was induced by using 2,4-dinitrophenyl (DNP)-modified lymphoid cells (DNP-LC) as tolerogen. Two kinds of Ts were found-those produced by DNP-LC syngeneic to the donor of the Ts (syninduced Ts), and those produced by DNP-LC allogeneic to the donor of Ts (alloinduced Ts). Studies employing congenic resistant mouse strains indicated that recognition of DNP-modified-major histocompatibility region determinants on the tolerogenic DNP-LC was essential for the induction of both types of Ts. Non-H-2 genetic background was irrelevant to Ts induction. Mapping studies indicated that induction of both syninduced and alloinduced Ts was associated with recognition of DNP-modified-MHC region determinants which map to the right of the H-2G region (i.e., H-2D gene products). Tolerization of donor mice with DNP-LC which were H-2D region compatible, but not with H-2K or I region compatible DNP-LC, was both sufficient and required for the induction of hapten-specific syninduced Ts. Tolerization of donor mice with DNP-LC which were incompatible only at the H-2D region was sufficient for the induction of alloinduced Ts. These Ts were capable of suppressing recipient mice only if the recipients shared the H-2D region with the strain providing the DNP-LC tolerogen, and were not capable of suppressing recipients sharing all but the H-2D region with the tolerogen.

Animals↗
PubMed1978

Suppressor T cell mechanisms in contact sensitivity. II. Afferent blockade by alloinduced suppressor T cells.

We investigated the mechanism(s) by which MHC-restricted suppressor T cells (Ts) induced by i.v. injection of allogeneic DNP-modified lymphoid cells (alloinduced Ts) suppress the DNFB contact sensitivity response. It was shown that alloinduced Ts acted only during the early phases (afferent limb) of sensitization. They were incapable of suppressing previously sensitized recipients or of inhibiting the expression of DNFB-immune LN cells when co-transferred into normal recipients. The target of alloinduced Ts seems to be cell proliferation, i.e., inhibition of antigen-induced cell proliferation (DNA synthesis) in Ts recipient mice. The failure of recipients of alloinduced Ts to generate DNFB-immune LN cells capable of transferring contact sensitivity to normal recipients also suggests that these Ts act by preventing the development of an expanded clone of mature immune T cells. The suppressive effects of alloinduced Ts also were inhibited by prior in vitro treatment with anti-TNP serum. The data are discussed in terms of current models of suppression, and are compared to mechanisms of suppression in other contact sensitivity models.

Animals↗
PubMed1977

Suppressor cells in tolerance to contact sensitivity active against hapten-syngeneic and hapten-allogeneic determinants.

Genetic restrictions in generation and expression of hapten-specific suppressor cells for contact sensitivity were found. Dinitrophenol- (DNP) or trinitrophenol-modified mouse spleen cells (SC) induced suppressors in donors able to transfer suppression to normal recipients. When allogeneic DNP-SC were injected into BALB/c mice, cells were generated which were suppressive only in the allogeneic strain providing the DNP-SC. In contrast, when DNP-BALB/c-SC were injected into BALB/c mice, suppressors were generated which were active both in BALB/c and in allogeneic mice (e.g., CBA). This apparent absence of syngeneic major histocompability complex restriction may be explained by cross reactive T-cell receptors which are VH gene products.

Animals↗
PubMed1977

H-2 restriction of suppressor T-cell induction by hapten-modified lymphoid cells in tolerance to 1-fluoro-2,4-dinitrobenzene contact sensitization.

Studies using hapten-modified lymphoid cells as tolerogens for 1-fluoro-2,4-dinitrobenzene contact sensitization have shown that BALB/c(H-2d) mice can be made phenotypically tolerant by dinitrophenyl (DNP) on either syngeneic or allogeneic mouse lymphoid cells (DNP-LC). However, suppressor T-cell induction (Ts) in these mice (as demonstrated by adoptive transfer to syngeneic recipients) was restricted to H-2 identity between the DNP-LC and the donor mouse. It was also shown that identity at the right end of the H-2 complex was sufficient for Ts induction. In addition, this restriction was also demostrated in CBA (H-2 K) mice and for tolerance in the 1-chloro-2,4,6-trinitrobenzene contact sensitivity system using trinitrophenyl-modified lymphoid cells.

Animals↗
PubMed1977

A splenic requirement for the generation of suppressor T cells.

Tolerance to contact sensitization with DNFB may be induced by DNBSO3. This specific unresponsiveness may occur via one or both of two mechanisms--production of suppressor T cells or clone inhibition. We investigated the role of the spleen in this unresponsiveness. Splenectomized mice may be tolerized by i.v. injection of DNBSO3, but they are incapable of serving as donors of lymph node cells for transfer of tolerance to normal recipients. Kinetic studies indicated that the spleen must be present at least three days after tolerization in order to permit development of a significant number of suppressor cells in the peripheral lymph nodes. We interpret these results to indicate that 1) clone inhibition does not require the spleen, 2) the generation of suppressor T cells is dependent on the presence of the spleen, and 3) it is likely that tolerogens in this system induce suppressor cells in the spleen and some of these cells or their products leave the spleen to reach the peripheral lymph nodes.

Animals↗
PubMed1977

Immune suppression with supraoptimal doses of antigen in contact sensitivity. I. Demonstration of suppressor cells and their sensitivity to cyclophosphamide.

Immunologic suppression was induced in a mouse model of contact sensitization to DNFB by using supraoptimal doses of antigen. In these studies, in vivo measurement of ear swelling as an indication of immunologic responsiveness correlated well with measurement of in vitro antigen-induced cell proliferation. This unresponsiveness was specific, since supraoptimal doses of DNFB did not interfere with the development of contact sensitivity to another contactant, oxazolone. The decrease in responsiveness is a form of active suppression, as lymphoid cells from supraoptimally sensitized donors transferred suppression to normal recipients. Furthermore, pretreatment with cyclophosphamide (Cy) reversed the suppression seen in supraoptimally sensitized animals but had no effect on the optimal sensitization regimen. These results indicate that supraoptimal doses of contactants can activate suppressor cells and that precursors of these cells are sensitive to Cy. Such suppressors regenerate within 7 to 14 days after Cy treatment. The ability of Cy pretreatment to affect supraoptimal sensitization without affecting optimal sensitization confirms other reports indicating that the observed results of Cy treatment depend critically upon the dose of antigen used.

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