The role of thymic stromal lymphopoietin in CD8+ T cell homeostasis.
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.
Rochman
Yrina
Y
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD20892-1674, USA.
Leonard
Warren J
WJ
D000818:Animals; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007136:Immunoglobulins; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D007136:Immunoglobulins; D019253:Proto-Oncogene Proteins c-bcl-2; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; C410591:Tslpr protein, mouse; C415350:interleukin-7 receptor, alpha chain; D051057:Proto-Oncogene Proteins c-akt; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse