Peripheral T cell-specific role of CDC42 of Rho GTPase family in T cell homeostasis and activation (P1286)

Abstract

Abstract We have reported that deletion of CDC42 of Rho GTPase family in T cells at early developmental stage (CD4-CD8-CD44-CD25+) affects T cell homeostasis by the use of CDC42flox/flox/LckCre mice. Here, we generated CDC42-deficient mice with selective expression of the Cre recombinase beginning at a late stage of T cell development (after positive selection of CD4+CD8+) using the distal promoter of the Lck (dLck) gene. As expected, CDC42 deficiency (CDC42flox/flox/dLckCre) did not affect T cell development. However, splenic CD8+, but not CD4+, T cells were significantly reduced in CDC42- deficient mice. Further analysis revealed that there was a marked increase of both proliferation and apoptosis in vivo in naïve CD8+ T cells from CDC42-deficient mice. IL-7/IL-7R signaling is critical for T cell survival. The expression of IL-7R in naïve CDC42-deficient CD8+ T cells was down-regulated. These changes were not significant in naïve CDC42-deficient CD4+ T cells. CDC42 deficiency impaired in vitro activation of both CD4+ and CD8+ T cells. Furthermore, CDC42 deficiency significantly reduced Th1 and Th2 cytokine secretion, but increased Th17 cytokine secretion from CD4+ T cells under non-polarized culture conditions. These results are significantly different from that obtained by using CDC42flox/flox/LckCre mice and suggest a peripheral T cell-specific role of CDC42 in T cell homeostasis and activation.