bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes.
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.
Pubmed ID: 1835668 RIS Download
Animals | Antigens, CD3 | Antigens, CD4 | Antigens, CD8 | Antigens, Differentiation, T-Lymphocyte | Antigens, Surface | Blotting, Western | Cell Death | Cell Survival | Dexamethasone | Flow Cytometry | Growth Hormone | Humans | Kinetics | Lymph Nodes | Mice | Mice, Inbred Strains | Mice, Transgenic | Protein-Tyrosine Kinases | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-bcl-2 | Proto-Oncogenes | Receptors, Antigen, T-Cell | Restriction Mapping | T-Lymphocyte Subsets | T-Lymphocytes