INHIBITION OF GAMMA-DELTA T-CELL DEVELOPMENT AND EARLY THYMOCYTE MATURATION IN IL-7- -MICE/

While early thymic T cell precursor populations and their maturational sequence have been recently identified, the signals driving different iation are unknown. While cytokines may play an integral role in T cel l development, various mouse models rendered genetically deficient for specific cytokines do not display abnormalities in T cell development , Recently, we have generated IL-7 -/- mice and reported that IL-7 pla ys a unique and nonredundant role in lymphopoiesis, These mice display ed a 10- to 20-fold reduction in the total number of T and B cells. He re, we show that IL-7 -/- mice display a sharp reduction in both the f requency and absolute number of adult thymic gamma delta T cells while retaining normal frequencies of ap T cells. This defect in gamma delt a T cell production extends to peripheral organs as IL-7 -/- mice are essentially devoid of splenic and intestinal intraepithelial gamma del ta T cells, This aberrant phenotype was traced back to impaired fetal gamma delta T cell maturation. In the absence of IL-7, differentiation of immature V gamma 3(low)CD24(+) fetal B cells to mature V gamma 3(h igh)CD24(-) cells is inhibited. In contrast, NK cell maturation appear s to be only mildly affected in the absence of IL-7. To further clarif y the role of IL-7 in thymic development, detailed analysis of CD3(-)4 (-)8(-) thymic precursors was performed, A partial inhibition in the d ifferentiation of CD44(+)25(+) pro-T cells into CD44(-)25(+) pre-T cel ls was observed. Unexpectedly, the lack of IL-7 resulted in decreased expression of CD117 (c-kit) on both CD4(low) and pro-T cells, suggesti ng that IL-7 may influence the expression of other cytokine receptors involved in early hemopoietic development, Together, these data clarif y the developmental abnormalities during T cell development due to the absence of IL-7.