bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship.
Early death is the fate of most developing T lymphocytes. Because bcl-2 can promote cell survival, we tested its impact in mice expressing an E mu-bcl-2 transgene within the T lymphoid compartment. The T cells showed remarkably sustained viability and some spontaneous differentiation in vitro. They also resisted killing by lymphotoxic agents. Although total T cell numbers and the rate of thymic involution were unaltered, the response to immunization was enhanced, consistent with reduced death of activated T cells. No T cells reactive with self-superantigens appeared in the lymph nodes, but an excess was found in the thymus. These observations, together with previous findings on B cells, suggest that modulated bcl-2 expression is a determinant of life and death in normal lymphocytes.
Strasser
A
A
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital Post Office, Victoria, Australia.
Harris
A W
AW
Cory
S
S
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001386:Azides / Q000494:pharmacology; D016923:Cell Death; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003433:Crosses, Genetic; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005720:Gamma Rays; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes; D019810:Sodium Azide; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D000954:Antigens, Surface; D001386:Azides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015759:Ionomycin; D003907:Dexamethasone; D019810:Sodium Azide; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate