Although chemotherapeutic regimens are effective for some types of cancers, immunotherapy is the most effective treatment for renal carcinoma. Thus, to further explore the utility of immunotherapy, we have focused our research efforts on the identification of the effects and the mechanisms of action of cytokine therapy on T-cell function. In this context, we have centered our attention on interleukin-7 (IL-7). Our previous work has shown that administration of IL-7 to normal and tumor-bearing mice increases T-cell numbers and function. Because dendritic cells (DC) have a critical role in T-cell activation we have speculated that DC may be involved in the enhanced T-cell function that occurs following IL-7 treatment. Therefore experiments have been initiated to examine the effect of IL-7 treatment on this important cell subset. Preliminary experiments demonstrate that IL-7 administration to normal mice results in a 6-fold increase in DC numbers in lymph nodes. Work is now in progress to determine the impact of IL-7 on DC function and the possible role DC have in enhancing T-cell function in IL-7- treated mice. We are also focusing on the mechamisms by which these T-cell effects occur. Our recent data demonstrate that IL-7 administration results in a 2-fold increase in bcl-2 protein and a 5-fold increase in bclx mRNA. These results suggest that the increase in T-cell numbers following IL-7 administration may be due, in part, to decreased cell turnover mediated through a bcl-family mechanism. Further work has found that T cells from IL-7-treated mice can respond to PMA alone without the need for the requisite induction of the calcium-mediated pathway. Moreover, activation of IL-7-treated T-cells is resistant to suppression by cyclosporin. These findings indicate that IL-7 initiates a signaling pathway that is both independent of the calcium-mediated pathway and able to synergize with the PKC-mediated pathway, suggesting similarities to the CD28 pathway. Taken in total, these data suggest that IL-7 may have efficacy in enhancing T-cell responses to immunization. Therefore, results from these studies will be useful in determining the potential of IL-7 as an adjuvant therapy to enhance vaccine-based T- cell-mediated antitumor responses. These findings further suggest that IL-7 may be useful in restoring T-cell deficiencies in HIV/AIDS patients.
