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

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 E mu 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-gamma delta (+) 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.