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.

Responder and nonresponder mice primed with poly-(L-glutamic acid,L-lysine,L-phenylalanine) (GLPhe), the response to which is under the control of immune response (Ir) genes, were used as a source of both types of helper T cells required for a T15 idiotype dominated T-dependent anti-phosphorylcholine (PC) response. It was found that the activity of one of the helper T cells needed for an anti-PC response was under major histocompatibility complex (MHC)-linked Ir gene control, and only GLPhe-primed responder mice could be used as a source of these cells. These T cells (ThMHC) whose presence is required for in vivo T-B collaboration are found in normal and anti-mu-treated mice, and their activity depends on the hapten being physically linked to the carrier molecule. By contrast, the activity of the second helper T cell (ThId) required for a T15-dominated anti-PC response was present in both GLPhe-primed responder and nonresponder mice. The ThId cell set that is missing or deficient in anti-mu treated mice can be restored by the addition of T cells from normal, carrier-primed donors and restimulating with the priming carrier. When T cells from GLPhe-primed donors are used as a source of ThId cells, both responder and nonresponder donors provide helper cells capable of inducing syngeneic B cells to produce a T15 dominated anti-Pc response. These results are interpreted to suggest that idiotype recognizing helper T cells (ThId) recognize antigen independent of known Ir gene products.

Section: Discussionmentioning

confidence: 99%

Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.

Bottomly¹,

Maurer²

1980

“…Thus, interaction of target cells with T-helper (2-5) or T suppressor (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) cells may depend on recognition of unique idiotypic determinants on the surface of the target cell. Furthermore, these interactions may be mediated by regulatory molecules that either bear the idiotype themselves (10,(15)(16)(17)(18) or are idiotype specific (10).…”

mentioning

confidence: 99%

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

Sherr¹,

Ju²,

Weinberger³

et al. 1981

Self Cite

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.

“…It is possible that T cells in the normal spleen cell population interact with the antigenspecific immune spleen cells to generate idiotype-specific suppressor T cells (21). It is known that Ig-associated structures on activated B cells can trigger Ly-1+2 -inducer cells to stimulate Ly-2 ÷ T suppressor activity (22).…”

Section: Discussionmentioning

confidence: 99%

Cellular interactions in immune regulation. Hapten-specific suppression by non-T cells and T cell-mediated reversal of suppression

Dekruyff¹,

Simonson²,

Siskind³

1981

The ability of lymphoid cells from immunized animals to regulate the response of naive B ceils to the immunizing hapten was studied. Mice were immunized with trinitrophenylated (TNP) bovine gamma globulin (BGG) in complete Freund's adjuvant, and their spleen cells were examined in vivo and in vitro for the presence of specific inhibitory activity. This activity was found to peak 1 wk after immunization, was active against TNP on both T-dependent (BGG) and T-independent (Ficoll and polyacrylamide beads) carriers, and was demonstrable both by mixed cell transfers and mixed cell culture experiments. In in vitro studies, it was shown that the inhibition of the response to TNP- polyacrylamide beads by immune spleen cells was mediated by a non-T cell, possibly a B cell, because the suppressor activity was enriched in a purified B cell preparation. A role for macrophages was not formally ruled out. A specific suppressor factor was produced in vitro by immune spleen cells cultured in the absence of antigen. The suppressor activity was modulated by T .cells because elimination of T cells from the normal spleen cell population decreased suppression; elimination of T cells from the immune spleen cell population did not effect suppression, but elimination of T cells from both the normal and immune spleen cell populations allowed the expression of marked specific suppression. Thus, T cells present in the normal spleen cell population augment the degree of suppression, whereas T cells present in the immune spleen cell population decrease the degree of suppression; that is, T cells present in the immune spleen cell population had the ability to specifically abrogate suppression ("abrosuppression") in a T-independent immune response. It is proposed that the response to a T- independent antigen is regulated by specific suppressor activity generated by a non-T cell and augmented by the interaction of this cell with a T cell. The suppressor activity can be blocked by a specific abrosuppressor T cell. It is suggested that, because suppressor activity appears dominant in the naive state of the immune system, the induction of specific abrosuppressor activity may be essential if an immune response is to take place.