Antigen-specific T-cell-mediated suppression. I. Induction of L-glutamic acid(60)-L-alanine(30)-L-tyrosine(10) specific suppressor T cells in vitro requires both antigen-specific T-cell-suppressor factor and antigen

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder mice but stimulates development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT plaque-forming cell responses to GAT complexed to methylated bovine serum albumin (MBSA). Extracts from lymphoid cells of GAT-primed but not control, nonresponder (DBA/1) mice contain a T-cell factor (GAT-TsF) that also specifically suppresses responses to GAT-MBSA by normal syngeneic spleen cells. The experiments reported in this communication demonstrate that: (a) extracts from all GAT-primed nonresponder mice tested contain GAT-TsF; (b) non-H-2 genes do not restrict the production of GAT-TsF; (c) all nonresponder strains of mice regardless of their non-H-2 genes are suppressed by GAT-TsF from all other strains bearing the nonresponder H-2p,q,s haplotypes; (d) suppression of GAT-MBSA responses by both syngeneic and allogeneic nonresponder spleen cells is mediated by a molecule encoded by the H-2 gene complex; and (e) both syngeneic and allogeneic nonresponder mice are suppressed by purified GAT-TsF that lacks immunoreactive GAT.

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Immunosuppressive factors from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10. IV. Lack of strain restrictions among allogeneic, nonresponder donors and recipients.

Kapp¹

1978

“…SF in many cases bear antigen-specific recognition units (5,7,8,19,20), are proteins derived from the suppressor T cell (5, 9), bear determinants encoded by the I-J subregion of the H-2 MHC (5,6,8,22), and do not bear conventional determinants present on Ig light or heavy chains constant regions (5,7,19). The potential mechanisms by which SF manifests suppression include the stimulation and generation of second-order suppressor T cells in as yet an incompletely understood manner (23,24) and/or alternatively, the direct inactivation of T helper (23) or T-effector cells (20).…”

Section: Aba-celt Induced Suppressor T-cells-derived-suppressor Factomentioning

confidence: 99%

Mechanisms of regulation of cell-mediated immunity. III. The characterization of azobenzenearsonate-specific suppressor T-cell-derived-suppressor factors.

Greene¹,

Bach²,

Benacerraf³

1979

Self Cite

Delayed type hypersensitivity to the hapten azobenzenearsonate (ABA) can be induced and suppressed by the administration of hapten-coupled syngeneic spleen cells by the appropriate route. Suppressor T cells stimulated by the intravenous administration of ABA-coupled spleen cells have been shown to produce a discrete subcellular factor(s) which is capable of suppressing delayed type hypersensitivity to azobenzenearsonate in the mouse. Such suppressor factors may be produced by the mechanical disruption of suppressor cells or by placing such suppressor cells in culture for 24 h. The suppressor factor(s) (SF) derived from ABA-specific suppressor cells exhibit biological specificity for the suppression of ABA delayed type hypersensitivity (DTH), but not trinitro-phenyl DTH, as well as the capacity to bind to ABA immunoadsorbents. Passage of suppressor factor(s) over reverse immunoadsorbents utilizing a rabbit anti-mouse F(ab')2 antiserum demonstrated that the antigen-specific T-cell derived SF does not bear conventional immunoglobulin markers. The suppressor factor(s) are not immunoglobulin molecules was further demonstrated by the inability of anti-ABA antibodies to suppress ABA DTH. Gel filtration of ABA suppressor factor(s) showed that the majority of the suppressive activity was present in a fraction with molecular weight ranging between 6.8 x 10(4) and 3.3 x 10(4) daltons. We also analyzed for the presence of determinants encoded by the H-2 major histocompatibility complex (MHC) and found that immunoadsorbents prepared utilizing antisera capable of interacting with gene products of the whole or selected gene regions of H-2 MHC, i.e., B10.D2 anti-B10.A and B10 anti-B10.A immunoadsorbents, retained the suppressive activity of ABA-SF. Elution of such columns with glycine HCl buffers (pH 2.8) permitted recovery of specific suppressive activity. Taken collectively such data supports the notion that suppressor T-cell-derived ABA suppressor factors have antigen-binding specificity as well as determinants controlled by the K end of the H-2 MHC. The distribution of strains capable of making SF has also been analyzed. The relationship of the antigen-binding specificity to VH gene products is discussed in this and the companion paper.

“…The treated cells were also enriched for IgM and IgG anti-SRBC PFC. Finally, experimental conditions were then chosen to use a treatment with anti-H-2 antiserum and complement to selectively eliminate the sIg-cells in educated The initial purpose of these experiments was to obtain a soluble factor from T cells that might induce T~ in analogy with the GAT system (13). Therefore, the in vitro SRBC-education protocol developed by Eardley and Gershon (16) was followed in an attempt to generate an SRBC-specific T~ source from which to prepare T~F.…”

Section: Sig+-educated Cells Are Responsible For Suppressionmentioning

confidence: 99%

“…Previous data have shown that Ts play a major role in the regulation of the Ir gene-controlled response to L-glutamic acid6°-L-alaninea°-L-tyrosine l° (GAT): GAT priming of nonresponder mice leads primarily to stimulation of GAT-specific T~ (11), which produce a soluble GAT TsF factor (GAT-TsF) (9) bearing I-region determinants and sharing a common idiotype with anti-GAT antibodies (12) that stimulates virgin T cells to develop T~ activity (GAT-T+F-induced Ts [T~]) (13). Furthermore, similar T~ and T+F can be obtained from responder lymphocytes, provided that antigen-presenting adherent cells are removed before GAT exposure (14).…”

mentioning

confidence: 99%

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

Zubler¹,

Cantor²,

Benacerraf³

et al. 1980

Self Cite

Powerful and often complex regulatory mechanisms that maintain homeostasis are a sine qua non of all carefully studied physiologic activities. Thus, it is not surprising that the immune system has evolved a sophisticated regulatory apparatus for preventing excessive responses to antigenic stimulation. The specific mechanisms so far described include (a) classical antibody feedback which is believed to operate by interference with cellular recognition of antigenic determinants (1, 2) and (b) development of suppressor T lymphocytes (Ts) 1 (3, 4), recognizing either antigenic (5) or idiotypic (6) determinants and functioning in part by the release of subcellular effector molecules (7-10). Until now, these two broad categories have been considered as largely independent pathways. However, it would seem likely that to most efficiently control humoral immunity, some interrelationship between these modalities would have evolved.The initial purpose of these studies was to further characterize the triggering and mode of action of suppressor T cells and T-suppressor factors (T+F). Previous data have shown that Ts play a major role in the regulation of the Ir gene-controlled response to L-glutamic acid6°-L-alaninea°-L-tyrosine l° (GAT): GAT priming of nonresponder mice leads primarily to stimulation of GAT-specific T~ (11), which produce a soluble GAT TsF factor (GAT-TsF) (9) bearing I-region determinants and sharing a common idiotype with anti-GAT antibodies (12) that stimulates virgin T cells to develop T~ activity (GAT-T+F-induced Ts [T~]) (13). Furthermore, similar T~ and T+F can be obtained from responder lymphocytes, provided that antigen-presenting adherent cells are removed before GAT exposure (14).