Deficient tumor‐specific immunity in old mice: in vivo mediation by suppressor cells, and correction of the defect by interleukin 2 supplementation in vitro but not in vivo

Abstract

The capacity of old (18-24 months) C57BL/6 mice to develop an immune reaction against MC-B6-1 fibrosarcoma cells was studied using in vivo adoptive transfer experiments (Winn assay) and in vitro T cell-mediated cytotoxicity test. Anti-tumor immunity was found to decline with age, as indicated by a decreased anti-tumor growth T cell activity. A suppressive activity was also found present in the splenic T cell population of old mice which can inhibit the in vivo generation of immune T cells in young mice. These suppressors, or their precursors, were resistant to cyclophosphamide treatment and were effective only when administered 3 days before the immunization of young mice. These mice developed immune T cells perfectly when the suppressors were administered 3 days after immunization, indicating that suppressors may act at an early phase of T cell activation. The protective activity of T cells in vivo correlated well with the in vitro T cell cytotoxicity for MC-B6-1 tumor cells, as both were depressed in old mice. Exogenous interleukin 2 (IL 2) addition during the 4-day culture period partially restored the low cytotoxic activity of old immunized lymphocytes, suggesting that specific clones were present but that a lack of IL 2 limited their expansion. However, in vivo supplementation with IL 2 administered after immunization did not increase the protection mediated by old immunized T cells but, rather, increased the suppression. This work demonstrates the presence of a T cell suppressive activity in the spleen of old mice but also indicates that precursors of cytotoxic cells are generated by the immunization. It seems that in vitro IL 2 addition increases cytotoxic cells while in vivo IL 2 administration amplifies the development of suppressor cells generated during immunization of aged mice.