Inhibition of Apoptosis and Augmentation of Lymphoproliferation inbcl-2Transgenic Fas/Fas Ligand-Defective Mice

Mice defective in Fas (CD95 or APO-1) or its ligand (lprorgldmice) 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 glucocorticoid-induced apoptosis. We backcrossedbcl-2transgenic mice tolprandgldmice to homozygosity to determine the effects of Bcl-2 overexpression. T cells in these mice were resistant to spontaneous and glucocorticoid-induced apoptosisin 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.