IL-7 administration alters the CD4 : CD8 ratio, increases T cell numbers, and increases T cell function in the absence of activation

IL-7 is vital for the development of the immune system and profoundly enhan ces the function of mature T cells. Chronic administration of IL-7 to mice markedly increases T cell numbers, especially CD8(+) T cells, and enhances T cell functional potential, However, the mechanism by which these effects occur remains unclear. This report demonstrates that only 2 days of IL-7 tr eatment is needed for maximal enhancement of T cell function, as measured b y proliferation, with a 6- to 12-fold increase in the proportion of CD4(+) and CD8(+) T cells in cell cycle by 18 h of ex vivo stimulation. Moreover, a 2-day administration of IL-7 in vivo increases basal proliferation by 4- and 14-fold in CD4(+) and CD8(+) T cells, respectively. These effects occur in the absence of cytokine production, increases in most activation marker s, and changes in memory markers. This enhanced basal proliferation is the basis for the increase in T cell numbers in that IL-7 induces an additional 60% and 85% of resting CD4(+) and CD8(+) T cells, respectively: to enter c ell cycle in mice given IL-7 for 7 days. These results demonstrate that in vivo administration of IL-7 increases T cell numbers and functional potenti al via a homeostatic, nonactivating process. These findings may suggest a u nique clinical niche for IL-7 in that IL-7 therapy may increase T cell numb ers and enhance responses to specific antigenic targets while avoiding a ge neral, nonspecific activation of the T cell population.