Auto-delayed-type hypersensitivity induced in immunodeficient mice with syngeneic modified self-antigens. II. Suppressor T cells control the autoimmune response.

Abstract

The control of the autoimmune response to modified self-antigens was explored, using immunodeficient mice injected with syngeneic trinitrophenylated spleen cells (TNP-SC) as an experimental model system. X-irradiated (250 rad) A mice injected with TNP-SC and footpad-challenged 7 to 14 days later with syngeneic lymphoblasts generated a delayed-type hypersensitivity (DTH) response that was expressed by footpad swelling measured 24 h, 48 h and 72 h later. Histopathological examination showed massive inflammatory infiltration in the soft tissues of the limbs with extensive necrosis. This was not observed in X-irradiated mice that received the lymphoblast challenge only. The immunological activity was transferred from the X-irradiated TNP-SC-immunized mice to naive recipients by T cells (Lyt-1+) and not by serum, thus excluding the possibility that the inflammatory reaction is mediated by antibodies. We have previously presented evidence that the differentiation status of the lymphoblasts, and not contaminants from the incubation media, was the determinant factor eliciting the DTH response of immunodeficient mice injected with TNP-SC. Since only syngeneic lymphoblasts were able to elicit the DTH response of immunodeficient mice injected with syngeneic TNP-SC, we suggested that immunological activity was directed against self-antigens, thus expressing an autoimmune reactivity. The ability of immunodeficient mice to generate syngeneic DTH was not restricted to the TNP hapten or to inbred A-strain mice. X-irradiated BALB/c mice injected with syngeneic penicillinated spleen cells and challenged with syngeneic lymphoblasts generated a significant DTH response, in contrast to X-irradiated BALB/c mice exposed to the challenge dose only. X-irradiated A mice injected with syngeneic TNP-SC and simultaneously reconstituted with syngeneic splenocytes failed to generate a DTH response after the lymphoblast challenge, indicating that the syngeneic DTH response is controlled by normal suppressor cells. The suppressor cells were characterized as T cells carrying I-Jk, Lyt-1+, Lyt-2+ and Lyt-3+ antigenic markers. The suppressor cells abrogated the syngeneic DTH response of immunodeficient mice injected with TNP-SC, even when transferred a few days after the induction of immunological activity, but not when transferred 1 h before the lymphoblast challenge, indicating that even the established immunological activity can be restrained. Various immunological aspects of these observations and the significance of the findings in illuminating human autoimmune disorders are considered.