Phenotypic and functional modifications of thymocytes during tumor growth

Thymocytes (T) from mice bearing the syngeneic tumor 3LL inhibit the immune response to SRBC by syngeneic splenocytes derived from control mice and cultured in Mishell and Dutton's antibody forming systems. T from control mice are devoid of this capacity but acquire it after in vitro incubation with tumor cells. It has been shown that metabolites of arachidonic acid (PGE-2, LTB-4 and LTC-4) synthesized in excess by tumor cells act as mediators for the acquisition of the above capacity by thymic cells in vitro. Surface phenotypical analysis by flow-cytometry demonstrated that in the thymus of tumor bearing mice the proportion of both single positive thymocytes (L3T4+/LY2- and L3T4-/LY2+) and of double negative thymocytes (L3T4-/LY2-) increased with a parallel decrease in the proportion of double positive cells (L3T4+/LY2+). In the mean time the total number of thymocytes markedly decreased. An attempt was done to mimic in vitro what happens in vivo. For this purpose T from control mice were incubated with conditioned culture medium in which 3LL cells had grown or with arachidonic acid metabolites. After one or the other of these treatments T from control mice did not modify their phenotypic antigenic pattern but acquired the capacity to negatively interfere with the in vitro immune response of normal spleen cells to SRBC. Since serum from tumor bearing mice contains large amounts of PGE-2, LTB-4 and LTC-4 we tested its effects on normal syngeneic T. Serum from tumor bearing mice, but not serum from normal mice, induces T from control syngeneic animals to acquire both immunosuppressive capacity and differentiation pattern clusters similar to those that characterize T derived from the thymus of tumor bearing mice. We demonstrated that metabolites of arachidonic acid are active as inducers of immunosuppressive capacity in T. On the other hand, a yet unknown factor present in serum of tumor bearing mice plays a role as inducer of differentiation of these cells.