Abstract
The vast majority of cortical thymocytes die during T cell development while those that survive this selective process accumulate in the medulla. bcl-2, an inner mitochondrial membrane protein, has been shown to inhibit apoptosis in certain cell lines. In the thymus, bcl-2 is regionally localized to the mature T cells of the medulla. To assess the role of bcl-2 in the programmed death of thymocytes, we generated transgenic mice that redirected bcl-2 expression to cortical thymocytes. bcl-2 protected immature CD4+8+ thymocytes from glucocorticoid, radiation, and anti-CD3-induced apoptosis. Moreover, bcl-2 altered T cell maturation, resulting in increased percentages of CD3hi and CD4-8+ thymocytes. Despite this, clonal deletion of T cells that recognize endogenous superantigens still occurred. This transgenic model indicates that multiple death pathways operate within the thymus that can be distinguished by their dependence on bcl-2.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Differentiation, T-Lymphocyte / immunology
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Antigens, Surface / analysis
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Blotting, Western
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CD3 Complex
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CD4 Antigens / immunology
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CD8 Antigens / immunology
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Cell Death*
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Cell Survival*
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Dexamethasone / pharmacology
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Flow Cytometry
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Growth Hormone / genetics
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Humans
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Kinetics
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Lymph Nodes / immunology
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Mice
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Mice, Inbred Strains
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Mice, Transgenic
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Protein-Tyrosine Kinases / genetics
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogenes*
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Receptors, Antigen, T-Cell / immunology
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Restriction Mapping
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T-Lymphocyte Subsets / immunology
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T-Lymphocytes / cytology*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
Substances
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Antigens, Differentiation, T-Lymphocyte
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Antigens, Surface
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CD3 Complex
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CD4 Antigens
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CD8 Antigens
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Antigen, T-Cell
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Dexamethasone
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Growth Hormone
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Protein-Tyrosine Kinases