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PMID:7602121
| Citation |
Tamura, A and Yui, K (1995) Age-dependent reduction of Bcl-2 expression in peripheral T cells of lpr and gld mutant mice. J. Immunol. 155:499-507 |
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| Abstract |
Autoimmune-prone lpr and gld mice carry defects in the apoptosis-mediating cell surface molecule Fas and its ligand, respectively. These mice develop lymphadenopathy because of an age-related accumulation of nonmalignant CD4- CD8- T cells in the peripheral lymphoid organs, suggesting a role for Fas-mediated apoptosis in peripheral T cell homeostasis. However, these accumulating cells are more susceptible to apoptosis ex vivo than peripheral T cells from control mice. To investigate the influence of additional regulatory elements on defects in the Fas-mediated apoptosis pathway, we analyzed the expression of Bcl-2 protein, a repressor of apoptosis, in T cells of lpr and gld mice. The expression levels of Bcl-2 in peripheral T cells of aged lpr and gld mice were significantly reduced when compared with their normal counterparts. Bcl-2 expression decreased with age in peripheral T cells, but not in thymocytes, suggesting that down-regulation of Bcl-2 protein occurs in the periphery. Analysis of T cell subsets indicated that CD4+ and CD4- CD8- T cells expressed significantly reduced levels of Bcl-2, whereas CD8+ cells maintain high levels of Bcl-2 expression. However, all peripheral T cell subsets including CD8+ cells were susceptible to glucocorticoid-induced apoptosis, indicating that there is no direct correlation between the levels of Bcl-2 expression and susceptibility to glucocorticoid-induced apoptosis. These studies suggest the presence of complex regulatory mechanisms for lymphocyte apoptosis and survival. |
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| Keywords |
Age Factors; Animals; Apoptosis/drug effects; CD4-CD8 Ratio; Cell Survival/drug effects; Cells, Cultured; Dexamethasone/pharmacology; Flow Cytometry; Lymph Nodes/cytology; Mice; Mice, Inbred C3H; Mice, Mutant Strains; Proto-Oncogene Proteins/analysis; Proto-Oncogene Proteins/biosynthesis; Proto-Oncogene Proteins c-bcl-2; T-Lymphocytes/chemistry; Thymus Gland/cytology |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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