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

LA Geiselhart, CA Humphries, TA Gregorio… - The Journal of …, 2001 - journals.aai.org
LA Geiselhart, CA Humphries, TA Gregorio, S Mou, J Subleski, KL Komschlies
The Journal of Immunology, 2001journals.aai.org
IL-7 is vital for the development of the immune system and profoundly enhances 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 treatment is needed for maximal enhancement of T cell function, as measured by
proliferation, with a 6-to 12-fold increase in the proportion of CD4+ and CD8+ T cells in cell …
Abstract
IL-7 is vital for the development of the immune system and profoundly enhances 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 treatment is needed for maximal enhancement of T cell function, as measured by 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 markers, 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 cell 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 potential via a homeostatic, nonactivating process. These findings may suggest a unique clinical niche for IL-7 in that IL-7 therapy may increase T cell numbers and enhance responses to specific antigenic targets while avoiding a general, nonspecific activation of the T cell population.
journals.aai.org