INHIBITION OF APOPTOSIS AND AUGMENTATION OF LYMPHOPROLIFERATION IN BCL-2 TRANSGENIC FAS FAS LIGAND-DEFECTIVE MICE/

Mice defective in Fas (CD95 or APO-1) or its ligand (lpr or gld mice) develop age-dependent lymphadenopathy and systemic autoimmune disease. T cells accumulating in the lymph nodes of these mice express reduced levels of Bcl-2 protein and are susceptible to spontaneous and glucoc orticoid-induced apoptosis, We backcrossed bcl-2 transgenic mice to lp r and gld mice to homozygosity to determine the effects of Bcl-2 overe xpression, T cells in these mice were resistant to spontaneous and glu cocorticoid-induced apoptosis in vitro, Moreover, the accumulation of CD4(-)CD8(-) T cells in the lymph nodes and the spleens was augmented, suggesting that a Bcl-2-dependent mechanism regulating the number of T cells residing in the peripheral lymphoid organs in addition to the Fas mediated pathway exists. (C) 1996 Academic Press, Inc.