A role for thymic stromal lymphopoietin in CD4+ T cell development

Amin Al-Shami, Rosanne Spolski, John Kelly, Terry Fry, Pamela L. Schwartzberg, Akhilesh Pandey, Crystal L. Mackall, Warren J. Leonard

Research output: Contribution to journalArticle

178 Scopus citations

Abstract

Thymic stromal lymphopoietin (TSLP) signals via a receptor comprising the interleukin (IL)-7 receptor α chain and a distinctive subunit, TSLP receptor (TSLPR), which is most related to the common cytokine receptor γ chain, γc. We have generated TSLPR knockout (KO) mice and found that although these mice had normal lymphocyte numbers, γc/ TSLPR double KO mice had a greater lymphoid defect than γcKO mice. This indicates that TSLP contributes to lymphoid development and accounts for some of the residual lymphoid development in γcKO mice and presumably in patients with X-linked severe combined immunodeficiency. Injection of TSLP into γcKO mice induced the expansion of T and B cells. Moreover, sublethally irradiated TSLPR KO mice showed weaker recovery of lymphocyte populations than wild-type (WT) littermates, even when neutralizing anti-IL-7 antibodies were injected. Interestingly, TSLP preferentially stimulated the proliferation and survival of CD4+ single positive thymocytes and peripheral T cells in vitro. Additionally, CD4+ T cells from TSLPR KO mice expanded less efficiently than WT CD4+ T cells in irradiated hosts, and TSLP preferentially expanded CD4+ T cells both in vitro and in vivo. Thus, as compared with other known cytokines, TSLP is distinctive in exhibiting a lineage preference for the expansion and survival of CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)159-168
Number of pages10
JournalJournal of Experimental Medicine
Volume200
Issue number2
DOIs
StatePublished - Jul 19 2004

Keywords

  • CD8 T cells
  • IL-7
  • Knockout mice
  • SCID
  • Thymocyte development

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Al-Shami, A., Spolski, R., Kelly, J., Fry, T., Schwartzberg, P. L., Pandey, A., Mackall, C. L., & Leonard, W. J. (2004). A role for thymic stromal lymphopoietin in CD4+ T cell development. Journal of Experimental Medicine, 200(2), 159-168. https://doi.org/10.1084/jem.20031975