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

Abstract

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.

Antigen- and receptor-driven regulatory mechanisms. III. Induction of delayed type hypersensitivity to azobenzenearsonate with anti-cross-reactive idiotypic antibodies.

“…In earlier studies, we had demonstrated that intravenous injection of anti-CRI antibodies preferentially activates suppressor T cells (20). Furthermore, pretreatment of animals with low doses of cyclophosphamide (Cy) eliminated the ability of the anti-CRI antibodies to induce suppression (20). However, it is now well established that the outcome of many immunological responses depends upon the doses of antigen employed, the manner it is administered, and the status of the host.…”

“…In earlier studies, we had demonstrated that intravenous injection of anti-CRI antibodies preferentially activates suppressor T cells (20). Furthermore, pretreatment of animals with low doses of cyclophosphamide (Cy) eliminated the ability of the anti-CRI antibodies to induce suppression (20).…”

“…Extensive information is available concerning the humoral immune response to ABA (19). In our earlier studies, we have demonstrated that anti-idiotypic antibodies to the major cross-reactive idiotype (CRI) associated with anti-ABA antibodies in A/J mice, when injected intravenously into normal A/J mice will stimulate ABA-specific suppressor T-cell responses (20). Moreover, these suppressor T cells bear CRI idiotypic determinants on their surface.…”

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

“…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).…”

Suppression of Hen Egg‐White Lysozyme (HEL)‐Specific Delayed‐Type Hypersensitivity Responses in Mice by Suppressor T Cells after Neonatal Administration of Anti‐Idiotypic Antibodies

“…Up to now, however, in most of the systems for the study of the biological effects of anti-Id antibodies, simple haptens or carbohydrates were employed as model antigens (3,5,11,30,31,34), notwithstanding the fact that the proteins are known as universally important antigens.…”