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The Role of Thymic Stromal Lymphopoietin in CD8⁺ T Cell Homeostasis¹

Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892

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 -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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health.

² Address correspondence and reprint requests to Dr. Warren J. Leonard, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674. E-mail address: wjl{at}helix.nih.gov

³ Abbreviations used in this paper: TSLP, thymic stromal lymphopoietin; 7-AAD, 7-aminoactinomycin D; DC, dendritic cell; KO, knockout; WT, wild type.