PMID:11359801

Citation	Ohteki, T, Maki, C and Koyasu, S (2001) Overexpression of Bcl-2 differentially restores development of thymus-derived CD4-8+ T cells and intestinal intraepithelial T cells in IFN-regulatory factor-1-deficient mice. J. Immunol. 166:6509-13
Abstract	Mice lacking IFN-regulatory factor (IRF)-1 have reduced numbers of mature CD8+ T cells within the thymus and peripheral lymphoid organs, suggesting a critical role of IRF-1 in CD8(+) T cell differentiation. Here we show that endogenous Bcl-2 expression is substantially reduced in IRF-1(-/-)CD8+ thymocytes and that introduction of a human Bcl-2 transgene driven by Emu or lck promoter in IRF-1(-/-) mice restores the CD8(+) T cell development. Restored CD8+ T cells are functionally mature in terms of allogeneic MLR and cytokine production. In contrast to thymus-derived CD8+ T cells, other lymphocyte subsets including NK, NK T, and TCR-gammadelta(+) intestinal intraepithelial lymphocytes, which are also impaired in IRF-1(-/-) mice, are not rescued by expressing human Bcl-2. Our results indicate that IRF-1 differentially regulates the development of these lymphocyte subsets and that survival signals involving Bcl-2 are critical for the development of thymus-dependent CD8+ T cells.
Links	PubMed
Keywords	Animals; CD8-Positive T-Lymphocytes/cytology; CD8-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/metabolism; Cell Differentiation/genetics; Cell Differentiation/immunology; Cell Survival/genetics; Cell Survival/immunology; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Gene Expression Regulation/immunology; Gene Transfer Techniques; Humans; Interferon Regulatory Factor-1; Interferon-gamma/biosynthesis; Interferon-gamma/physiology; Intestinal Mucosa/cytology; Intestinal Mucosa/immunology; Intestinal Mucosa/metabolism; Killer Cells, Natural/immunology; Lymphocyte Activation/genetics; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Phosphoproteins/deficiency; Phosphoproteins/genetics; Phosphoproteins/physiology; Proto-Oncogene Proteins c-bcl-2/administration & dosage; Proto-Oncogene Proteins c-bcl-2/biosynthesis; Proto-Oncogene Proteins c-bcl-2/genetics; Receptors, Antigen, T-Cell, gamma-delta/biosynthesis; T-Lymphocyte Subsets/cytology; T-Lymphocyte Subsets/immunology; T-Lymphocyte Subsets/metabolism; Thymus Gland/cytology; Thymus Gland/immunology; Transgenes/immunology
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