Summary:The purpose of the studies being described was to determine if interleukin‐2 (IL‐2) administeredin vivocan induce the growth and increase the number of antigen‐activated T cells, and thereby augment specific T cell functionin vivo.Initial experiments examined thein vivogrowth of adoptively transferred T cells previously cultured long term with IL‐2, sincein vitrosuch long‐term cultured T cells are exquisitely dependent on exogenous IL‐2 for proliferation and survival. To identify and quantify donor T cellsin vivo, experiments were performed with donor and host mice congenic for the T cell marker Thy 1. Host mice receiving congenic long‐term cultured immune T cells were inoculated daily with purified IL‐2 beginning on the day of cell transfer, and donor T cells within host ascites, spleen, and lymph nodes were enumerated at selected points in time. The experiments demonstrated that exogenous IL‐2 inducedin vivogrowth of long‐term cultured T cells proportional to the dose of IL‐2 administered. Similar IL‐2 regimens induced thein vivogrowth and augmented the function of donor T cells that had been activated to express IL‐2 receptorsin vitroby 5‐day culture with antigen but had not been cultured with exogenous IL‐2. Thus, prior adaptation to growth with exogenous IL‐2in vitrois not necessary to render T cells responsive to IL‐2in vivo. In contrast to long‐term cultured T cellsin vivo(which died rapidlyin vivowithout exogenous IL‐2), noncultured donor T cells proliferatedin vivoin response to antigen. This proliferation presumably reflected endogenous production of IL‐2 and the administration of exogenous IL‐2 failed to augment thein vivogrowth of noncultured donor T cells. Additionally, certain IL‐2 regimens appeared to decrease the magnitude of such antigen‐driven immune responses. Thus, there may be situationsin vivoin which the administration of IL‐2 negatively influences cell‐mediated immunity. Studies to examine the effect of IL‐2 on T cell functionin vivodemonstrated that IL‐2 regimens that induced growth of T cellsin vivoalso augmented the ability of adoptively transferred donor T cells to eradicate disseminated murine leukemia. Thus, the results suggest that IL‐2 may have significant therapeutic potential forin vivostimulation of T cell responses that are relatively deficient in the production of endogenous IL‐2.