The magnitude of cell-mediated immunity in vivo is in part a reflection of the number of immune T lymphocytes present. Interleukin 2 (IL 2), induces the replication of antigen-activated T lymphocytes and thereby provides a potential means for rendering weak immune responses strong. T lymphocytes immune to murine leukemia can be grown in vitro in response to IL 2 and are able to mediate a specific, cell dose-dependent, effect in vivo in therapy when inoculated into hosts bearing disseminated tumor. In vitro, such cultured T lymphocytes are exquisitely dependent upon exogenous IL 2 for the induction of proliferation and survival. In vivo, the administration of IL 2 induces the growth of similar cultured T lymphocytes and, as a consequence, can further increase their efficacy in therapy. The experiments outlined in the current proposal will further develop and evaluate techniques to generate effector T cells in vitro. Methods for isolating, expanding, cloning, and evaluating tumor-reactive T lymphocytes of varied functional subsets will be utilized in order to characterize the different types of immune T lymphocytes grown and to determine how they might be best used in the therapy of advanced disseminated murine leukemia. Thus, ultimately, it may be possible to exploit even weak immune responses to selectively produce large numbers of effector T cells of the desired specificity and function for therapy. Although no human studies are presented in this application, the long-term goal of the proposed research is to develop laboratory approaches to specific immunotherapy which might be applicable to man.
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