ADMINISTRATION OF RECOMBINANT HUMAN IL-7 TO MICE ALTERS THE COMPOSITION OF B-LINEAGE CELLS AND T-CELL SUBSETS, ENHANCES T-CELL FUNCTION, AND INDUCES REGRESSION OF ESTABLISHED METASTASES

These studies investigate the effects of exogenously administered reco mbinant human IL-7 (rhIL-7) on mouse leukocyte subsets in vivo in norm al and tumor-bearing mice. The administration of rhIL-7 to normal mice caused a pronounced leukocytosis (three- to fivefold increase over ba ckground) in the spleen and lymph nodes, with B-lineage and T cells, N K cells, and macrophages all being increased. CD8(+) T cells increased disproportionately, such that the CD4 to CD8 ratio decreased dramatic ally. The rhIL-7-induced effects were dose-dependent, increased with d uration of treatment, and were reversible after cessation of rhIL-7 ad ministration. T cell number increases after rhIL-7 treatment were prim arily a result of an expansion of the peripheral T cell population. Im portantly, splenocytes from rhIL-7-treated mice have enhanced prolifer ative responses to various T cell stimuli in vitro and were able to po tentiate an allogeneic CTL response in vivo. The rhIL-7-induced change s in T cell number and the CD4 to CD8 ratio also were observed in mice bearing early Renca renal adenocarcinoma pulmonary metastases, and th ese changes coincided with up to a 75% reduction in pulmonary metastas es. Overall, these results demonstrate that the administration of rhIL -7 to mice profoundly increases the number of B and T cells, and reduc es the number of pulmonary metastases. The results also suggest that I L-7 may be useful for restoring lymphoid subsets in immunosuppressed h osts and in enhancing T cell-mediated immune responses. Such effects m ay be useful in the treatment of microbial diseases and cancer.