Suppressor factor from tumor-allosensitized spleen cells—Its effect on in vitro proliferation of tumor cells and in vivo skin allograft survival

Abstract

C57BL/6 mice are sensitized ip with allogeneic P-815 mastocytoma cells. Fifteen days later the spleen cells of the sensitized mice are used in the production of suppressor factor or treated with mitomycin and used as suppressor cells. Sensitized spleen cells incubated with the specific alloantigen (DBA/2 m-treated spleen cells) release suppressor factor (SF) 2 2 Abbreviations used: AA m, MLC cultures with syngeneic responding and mitomycin-treated (m) stimulating cells; AB m, MLC cultures with allogeneic responding and mitomycin-treated (m) stimulating cells; CI, cytotoxic index; CML, cell-mediated lysis; Con A, concanavalin A; cpm ± SE, counts per minute ± standard error; [ 3H]TdR, tritiated thymidine; LPS, lipopolysaccharide; m, mitomycin treated; MLC, mixed lymphocyte culture; NS, nonsensitized spleen; PHA, phytohemagglutinin; SF, suppressor factor; SI, stimulation index; SS, sensitized spleen; T cell, thymus-derived lymphocyte. which inhibits cell proliferation in mixed lymphocyte culture (MLC) as well as the in vitro generation of cytotoxic cells (CML). SF is most effective when added eary during MLC. SF also inhibits mitogen responsiveness of normal spleen cells. In addition to inhibiting lymphocyte function in vitro, suppressor cells as well as SF inhibit the in vitro proliferation of tumor cells. This inhibition is specific for the tumor to which the suppressor cells are induced. The inhibition of tumor cell proliferation is not due to the presence of cytotoxic cells in the spleen of the tumor-allosensitized mice. Suppressor cells from neonatal mice do not inhibit the in vitro proliferation of tumor cells. SF injected iv into C57BL/6 mice decreases the mixed lymphocyte reactivity of the host spleen cells and decreases the ability of the host to reject skin allografts. We interpret these data to suggest that tumor-allosensitized spleen cells, and the SF they produce, not only affect lymphocyte function but also inhibit tumor cell proliferation. This dual effect of suppressor cells could be an important part of the immune surveillance against tumors.