Suppression of idiotype and generation of suppressor T cells with idiotype-conjugated thymocytes.

Abstract

Inoculation of A/J mice with syngeneic thymocytes conjugated with specifically purified A/J anti-phenylarsonate (anti-Ar) antibodies, selectively suppressed the subsequent synthesis of those anti-Ar antibodies which carry the major cross-reactive idiotype. High titers of anti-Ar antibodies were produced upon subsequent immunization but in most mice the idiotype was undetectable. Suppression similarly occurred in F1(A/J X BALB/c) and in C.AL-20 mice. Although some mice were suppressed when unconjugated antibody was injected, the suppressive effect was much more pronounced, particularly in the F1 and C.AL-20 recipients, when the antibody was coupled to thymocytes. The state of suppression could be adoptively transferred with T cells to mildly irradiated syngeneic recipients. A population enriched for B cells had little if any suppressive effect. There was no requirement for antigen in the generation of suppressors. Thymocytes conjugated with antibody did not induce idiotype-specific suppression in mice that had been recently challenged with antigen. Thymocytes from BALB/c and C57BL/10 mice were effective carriers for the anti-Ar antibodies, i.e., there was no evidence for H-2 restriction. The experiments demonstrate the feasibility of suppressing idiotype production and generating idiotype-specific suppressor T cells without the use of anti-idiotypic antibody or antigen.

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

“…In most studies of idiotype-specific suppression of a B cell response, suppressor cells have been induced by administration of anti-idiotypic antiserum (7,10,19), idiotype alone (4,20), or idiotype conjugated to syngeneic cells (9). The operation of such an idiotypic suppressor mechanism during the normal course of a humoral immune response would be more directly demonstrated if antigen-induced suppressor cells, acting in an idiotype-specific manner, could be elicited by antigen.…”

“…To explain the apparent idiotype specific restrictions of T-T and T-B cell collaboration the network theory has been expanded to encompass the interaction of lymphoid cells as well as antibodies (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). 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).…”

IgE class-restricted tolerance induced by neonatal administration of soluble or cell-bound IgE.

“…Determinants encoded by the major histocompatibility complex (MHC) played critical roles in presenting haptens to trigger precursor suppressor T cells, and the suppressor T cells thus induced were shown to be restricted to the hapten-MHC complex (35). Although the MHC appeared to play no role in presenting idiotype to precursor suppressor T cells (36)(37), nevertheless, idiotype-specific T suppressor cells must be Igh congenic to the idiotypic molecules' present syngeneic lymphocytes. In the system presented herein, the importance of MHC gene products, Igh gene products, or other cell-surface determinants on both presenting and responder cells must be assessed in future experiments.…”

“…This could mean that such determinants are involved either in presentation of the relevant IgE determinant(s) important in this mechanism or in the recognition of the IgE-conjugated spleen cells used. Syngeneic lymphocytes modified with hapten or particular idiotypes have been demonstrated to exert a potent negative regulatory effect on hapten-or idiotypespecific responses in other experimental systems (35)(36)(37). Determinants encoded by the major histocompatibility complex (MHC) played critical roles in presenting haptens to trigger precursor suppressor T cells, and the suppressor T cells thus induced were shown to be restricted to the hapten-MHC complex (35).…”

Induction of idiotype-specific suppressor T cells with antigen/antibody complexes.

“…Anti-Id Ts have been induced by a variety of experimental manipulations including the administration of anti-Id antibody (14,15), immunization with purified myeloma proteins in adjuvant (16), or by injection of idiotype-conjugated cells (17,18). In addition, idiotype-positive first order suppressor cells (Ts-1) or soluble factors derived from such cells have been shown to induce second order (Ts-2) suppressor cells that are antiidiotypie (42).…”