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 enhances function. Recent results from our laboratory demonstrate that IL-7 pretreatment allows T cells subsequently stimulated with anti-CD3 and anti-CD28 to enter the S-phase of cell cycle approximately 12 hours earlier than non-pretreated T cells. Moreover, preliminary data suggest that IL-7 pretreatment moves lymph node cells (70-85% T cells) to late G1 in the cell cycle as evidenced by increased levels of cyclin E and hyperphosphorylated Rb in these pretreated cells. In addition, while both CD4+ and CD8+ T cells pretreated with IL-7 enter S-phase earlier following subsequent stimulation, 2.5-fold more CD8+ T cells enter S- phase compared to CD4+ T cells. The preferential effects of IL-7 pretreatment on CD8+ T cells also is seen in enhanced cytokine production by 10-hours after subsequent stimulation. Specifically, IL-7 pretreatment increases the number of CD8+ cells that produce interferon-gamma in response to subsequent stimulation by 4-fold compared to controls. Whereas no increase was observed in the CD4+ T- cell subset.In other work, we have examined the effect of IL-7 pretreatment on cells that are important for the presentation of antigen to T-cells; a critical component for an effective T-cell response. Our data demonstrate that mice treated with IL-7 for seven days have a 5-fold increase in the number of lymph node dendritic cells. In addition, preliminary data suggest that this expansion does not occur through activation of dendritic cells. 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. - Animal models, cancer immunotherapy, Cytokines, interlenkin-7, T lymphocytes, Dendritic cells,
