THYMIC SELECTION AND PEPTIDE-INDUCED ACTIVATION OF T-CELL RECEPTOR-TRANSGENIC CD8 T-CELLS IN INTERLEUKIN-2-DEFICIENT MICE

The requirement for interleukin-2 (IL-2) in repertoire selection and p eripheral activation of CD8 T cells was tested in mice rendered IL-2 d eficient by gene targeting and expressing a transgenic T cell receptor (TcR) (F5) specific for influenza nucleoprotein (NP) 366-374 + H-2D(b ). Positive selection of the transgenic F5 TcR into the CD8 compartmen t proceeded normally. Both in vivo and in vitro, the antigenic peptide induced depletion of immature thymocytes and proliferation of mature CD8 T cells regardless of the presence of an intact IL-2 gene. In cont rast, cytotoxic T lymphocyte (CTL) activity was only generated by T ce lls from IL-2(+) F5 transgenic mice. Exogenous IL-2 was able to fully restore the CTL response of IL-2(-/-) responder cells in vitro. Thus, both in vivo and in vitro, clonal expansion of CD8 T cells can proceed in the absence of IL-2, whereas in peptide-immunized F5 transgenic mi ce, induction of cytotoxic effector function is IL-2 dependent.