Suppressor cell regulation of immune response to tumors: Abrogation by adult thymectomy

Abstract

The regulatory role of the adult thymus on the appearance of cytotoxic and suppressor T cells (thymus-derived lymphocytes) to allogeneic and autochthonous virus induced tumors in mice was investigated. C57BL/6 mice challenged with allogeneic P815 mastocytoma cells and complete Freund''s adjuvant failed to develop cytotoxic cells but instead developed suppressor T cells which inhibited cytotoxic T cell function. Adjuvant induced suppressor cells prevented the primary in vitro induction of cytotoxic T cells to P815 mastocytoma cells. Adult thymectomized animals, when challenged with adjuvant and allogeneic cells, had a normal cytotoxic response in vivo and their cells could not inhibit the generation of cytotoxic T cells in vitro. These studies suggested that the intact adult thymus was necessary for the induction of suppressor cells. Suppressor cells regulated cytotoxic T cell actvity in vivo and in vitro. Adjuvant could also prevent the normal immune response to virus induced tumors. BALB/c mice treated with murine sarcoma virus developed tumors which reached a maximal size by day 14 and then regressed. Sham thymectomized animals treated with virus and complete Freund''s adjuvant to generate suppressor cells died from progressive tumor growth. Thymectomized animals similarly treated had normal regression of tumor and survived. The adult thymus may regulate immune responsiveness by the export of suppressor T cells which regulate other T cell responses to allogeneic and tumor antigens.