Production of immunosuppressive factor(s) by a weakly immunogenic fibrosarcoma T 241

Earlier we have reported that the progressive growth of Lewis fibrosarcoma T241 in C57 BL/6J mice causes immunosuppression. Tumor-bearing mice were shown to possess suppressor T cells in the spleen and soluble immunosuppressive factors in the serum. The present study investigated the effect of supernatants from T241 cultures on the response of normal spleen cells to mitogens and antigens. When added to the cultures at time zero, these supernatants inhibited the proliferation responses induced with concanavalin A and phytohemagglutinin. The responses to allo-antigens in mixed lymphocyte cultures and cell-mediated lympholysis were also significantly suppressed (P less than 001). Each of these responses was suppressed in a dose-dependent manner. Predominantly associated with material possessing molecular weight of less than 10,000 daltons, the suppressive activity was completely lost by heating supernatants at 80 degrees C for 30 min. Thus, the presence of immunosuppressive materials in the culture fluids of T241 together with the occurrence of suppressor T cells and the humoral immuno-suppressive factor(s) in tumor-bearing mice are suggestive of a multifactorial mechanism whereby the growth of fibrosarcoma T241 causes immunodepression in the host.