Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice.
Signals from cytokine and antigen receptors play crucial roles during lymphocyte development. Mice lacking interleukin-7 receptor are lymphopenic, due to a defect in cell expansion at an early stage of differentiation, and the few mature T cells that develop in IL-7R-/- animals are functionally impaired. Both defects were rescued completely by overexpression of the anti-apoptosis protein Bcl-2. T cell progenitors lacking antigen receptor molecules are also blocked in differentiation and die, presumably because they fail to receive a positive signal via their pre-T cell receptor. Surprisingly, Bcl-2 did not promote survival or differentiation of T cells in rag-1-/- mice. These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2.
Maraskovsky
E
E
Department of Cellular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101, USA.
O'Reilly
L A
LA
Teepe
M
M
Corcoran
L M
LM
Peschon
J J
JJ
Strasser
A
A
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000276:immunology; D016654:Genes, RAG-1 / Q000235:genetics; D018398:Homeodomain Proteins; D006801:Humans; D015851:Interleukin-7 / Q000172:deficiency / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology; D016296:Mutagenesis / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D020395:Receptors, Interleukin-7; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000737:chemistry / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D019076:Transgenes / Q000276:immunology
D000941:Antigens; D015703:Antigens, CD; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015851:Interleukin-7; D008934:Mitogens; D019253:Proto-Oncogene Proteins c-bcl-2; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7; C064658:RAG-1 protein