The role of thymic stromal lymphopoietin in CD8+ T cell homeostasis

J Immunol. 2008 Dec 1;181(11):7699-705. doi: 10.4049/jimmunol.181.11.7699.

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

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Basophils / immunology
  • Basophils / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation*
  • Cell Survival / immunology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytokines / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Immunoglobulins
  • Immunologic Memory / genetics
  • Immunologic Memory / immunology
  • Lymphopenia / genetics
  • Lymphopenia / immunology
  • Lymphopenia / metabolism
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / immunology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / immunology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / immunology*
  • Receptors, Cytokine / metabolism
  • Receptors, Interleukin-7 / biosynthesis
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / immunology
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / immunology
  • STAT5 Transcription Factor / metabolism
  • Stromal Cells / immunology
  • Stromal Cells / metabolism
  • Thymic Stromal Lymphopoietin

Substances

  • Cytokines
  • Immunoglobulins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Cytokine
  • Receptors, Interleukin-7
  • STAT5 Transcription Factor
  • Tslpr protein, mouse
  • interleukin-7 receptor, alpha chain
  • Proto-Oncogene Proteins c-akt
  • Thymic Stromal Lymphopoietin
  • TSLP protein, mouse