Interleukin-2 induction of hapten-specific cytolytic T cells in nude mice

Abstract

In light of i) increasing evidence that the thymus guides the development and antigen recognition repertoire of cytotoxic T cells (CTL) and ii) the capacity of purified interleukin 2 (IL-2) to allow for the in vitro generation of CTL from nude mice, we investigated the ability of IL-2 to influence the in vitro generation of hapten-specific cytotoxicity from nude mouse spleen cell cultures. We found that stimulation of nude mouse splenocytes with trinitrophenol (TNP)-derivatized autologous or allogeneic spleen cells in the presence of IL-2 generated hapten-specific CTL. EFfector cells harvested from IL-2-supplemented cultures killed only TNP-derivatized target cells; however, the cytotoxicity observed was not restricted to a particular target histocompatibility type. This study confirms our previous observations that IL-2 has the capacity to induce growth of CTL from pre-T cell populations in the total absence of thymic influence. However, it is clear that the generation of H-2 restricted killing (recognition and lysis of cells bearing antigen presented solely in association with "self" H-2) probably requires further processing of pre-killer T cell populations by a thymus-derived differentiation signal. In addition, these studies provide further evidence that a major role of the thymus, in addition to programming effector T cell antigen recognition repertoire, may be its function to provide essential differentiation of the IL-2 producer T cell.