Expression of activated CDC42 induces T cell apoptosis in thymus and peripheral lymph organs via different pathways

CDC42, a Ras-related small GTP binding protein, is involved in diverse cell ular functions in lymphocytes. We generated transgenic mice expressing cons titutively active murine CDC42 (Q61L) under the control of the human CD2 pr omoter. Transgenic mice showed smaller thymi with a dramatic reduction of C D4(+)CD8(+), CD4(+) and CD8(+) thymocytes and with increase of CD4(-)CD8(-) thymocytes at CD25(-)CD44(+) and CD25(+) stage. A high percentage of the t ransgenic thymocytes were apoptotic, explaining the reduction of cellularit y and size of the thymus, Mature T cells (TCR alpha beta(+)) in peripheral lymph organs, spleen and lymph node, were also dramatically reduced, and ex hibited massive apoptosis, Expression of Fas and Fas ligand on both thymocy tes and peripheral T cells was upregulated in transgenic mice, but the incr eased apoptosis in the thymus was independent of Fas (CD95), whereas periph eral spleen and lymph node T cell apoptosis was Fas dependent. Thus, activa ted CDC42 triggers distinct apoptotic pathways in thymocytes and peripheral T cells.