Induction of cytotoxic T lymphocyte development from murine thymocytes by IL-1 and IL-6

Cytotoxic T lymphocytes (CTL) are believed to play an important role in the regression of advanced malignancies in response to adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer cells or tumor-infiltrating lymphocytes. Because the current limitations to the use of adoptive immunotherapy are the IL-2 dose-dependent toxicities and the difficulty in expanding the effector cell population, recent investigations have focused on the development of newer methods for generating CTL in vitro. IL-1 and IL-6 have been shown to synegistically promote thymocyte proliferation; however, their effect on CTL development has not been studied. We investigated the ability of these two cytokines to induce CTL development from immature thymocytes. Thymocytes from 5-week-old BALB c mice were cultured for 72 hours in the presence of Con A and recombinant IL-1, IL-6, or IL-1 plus IL-6. Cytotoxicity against ⁵¹Cr-labeled P815 target cells was then measured in the presence of submitogenic doses of PHA. Neither IL-1 nor IL-6 induced a significant number of CTL from immature thymocytes. However, these two cytokines synergistically induced maximal CTL development. The monoclonal antibody to IL-4 completely abrogated CTL development induced by IL-1 and IL-6, but antibody to the IL-2 receptor had no effect. The data suggest that IL-1 and IL-6 can provide an additional method for in vitro CTL generation in adoptive immunotherapy of advanced tumors.