Abstract
Mice lacking the common cytokine receptor gamma-chain (gamma c) exhibit severely compromised T cell development, with diminished Bcl-2 expression in mature (CD4+ or CD8+) thymocytes and peripheral T cells. Enforced expression of Bcl-2 in these mice partially rescued alpha beta T cell development but not gamma delta T cell development. Transgenic expression of the OVA-specific DO11.10 (DO10) TCR also could modestly increase thymocyte numbers, and T cells expressing the transgenic TCR (KJ1-26+ T cells) were found in the periphery. Interestingly, the presence of KJ1-26+ T cells was dependent on the MHC background and was seen in the moderate affinity H-2d/d background but not in the higher affinity H-2d/b background in gamma c-deficient mice. In contrast, KJ1-26+ T cells exist in the periphery in both the H-2d/d and H-2d/b backgrounds in DO10 transgenic gamma c wild-type mice. These results suggest that the importance of gamma c-dependent signals for T cell development differs depending on the affinity of TCR for MHC. Moreover, enforced expression of Bcl-2 had a much greater effect on the development of gamma c-deficient T cells expressing the DO10 TCR in the high affinity H-2d/b background than in the H-2d/d background, suggesting that gamma c-dependent Bcl-2 expression influences T cell development in a TCR/MHC-dependent manner.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD3 Complex / biosynthesis
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / metabolism
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Cell Cycle / genetics
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Cell Cycle / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Female
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H-2 Antigens / genetics
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H-2 Antigens / metabolism*
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Histocompatibility Antigen H-2D
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Lymphocyte Count
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / deficiency
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / metabolism*
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Receptors, Antigen, T-Cell, gamma-delta / biosynthesis
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Receptors, Cytokine / deficiency*
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Receptors, Cytokine / genetics
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Receptors, Interleukin-2 / analysis
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / pathology*
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Thymus Gland / metabolism
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Thymus Gland / pathology
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Transgenes / immunology
Substances
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CD3 Complex
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H-2 Antigens
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Histocompatibility Antigen H-2D
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Cytokine
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Receptors, Interleukin-2