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 glucocorticoid-induced apoptosis. We backcrossed bcl-2 transgenic mice to lpr and gld mice to homozygosity to determine the effects of Bcl-2 overexpression. T cells in these mice were resistant to spontaneous and glucocorticoid-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.
Tamura
A
A
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Katsumata
M
M
Greene
M I
MI
Yui
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003433:Crosses, Genetic; D003907:Dexamethasone / Q000494:pharmacology; D004351:Drug Resistance; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction; D013045:Species Specificity; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology; D019076:Transgenes; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D003907:Dexamethasone