Abstract
Thymic stromal lymphopoietin (TSLP) is a cytokine produced by stromal cells, epithelial cells, and basophils that acts on dendritic cells, mast cells, and CD4(+) T cells. The receptor for TSLP contains a TSLP-specific receptor chain (TSLPR) and the IL-7R alpha-chain. Although IL-7 critically controls the expansion and survival of naive and memory CD8(+) T cells, an action for TSLP on CD8(+) T cells has not been reported. We now demonstrate that CD8(+) T cells express TSLPR and that TSLP activates both STAT5 and Akt and induces Bcl-2 in these cells. Correspondingly, TSLP increases CD8(+) T cell survival in vitro as well as in wild-type and T-depleted mice in vivo, without altering the homeostatic proliferation of these cells. Moreover, TSLP can maintain CD8(+) T cells even in the absence of IL-7. Thus, our data reveal that TSLP contributes to CD8(+) T cell homeostasis in both normal and lymphopenic conditions.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Basophils / immunology
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Basophils / metabolism
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Proliferation*
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Cell Survival / immunology
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Cytokines / biosynthesis
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Cytokines / genetics
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Cytokines / immunology*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Epithelial Cells / immunology
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Epithelial Cells / metabolism
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Homeostasis / genetics
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Homeostasis / immunology*
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Immunoglobulins
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Immunologic Memory / genetics
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Immunologic Memory / immunology
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Lymphopenia / genetics
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Lymphopenia / immunology
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Lymphopenia / metabolism
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Mast Cells / immunology
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Mast Cells / metabolism
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Mice
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Mice, Knockout
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / immunology
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Proto-Oncogene Proteins c-akt / metabolism
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / immunology
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptors, Cytokine / genetics
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Receptors, Cytokine / immunology*
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Receptors, Cytokine / metabolism
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Receptors, Interleukin-7 / biosynthesis
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Receptors, Interleukin-7 / genetics
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Receptors, Interleukin-7 / immunology
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STAT5 Transcription Factor / genetics
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STAT5 Transcription Factor / immunology
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STAT5 Transcription Factor / metabolism
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Stromal Cells / immunology
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Stromal Cells / metabolism
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Thymic Stromal Lymphopoietin
Substances
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Cytokines
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Immunoglobulins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Cytokine
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Receptors, Interleukin-7
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STAT5 Transcription Factor
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Tslpr protein, mouse
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interleukin-7 receptor, alpha chain
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Proto-Oncogene Proteins c-akt
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Thymic Stromal Lymphopoietin
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TSLP protein, mouse