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Development of regulatory T cells requires IL-7R alpha stimulation by IL-7 or TSLP

  1. Author:
    Mazzucchelli, R.
    Hixon, J. A.
    Spolski, R.
    Chen, X.
    Li, W. Q.
    Hall, V. L.
    Willette-Brown, J.
    Hurwitz, A. A.
    Leonard, W. J.
    Durum, S. K.

  2. Author Address

    Durum, Scott K.] NCI, FCRDC, Mol Immunoregulat Lab, Canc & Inflammat Program,Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Spolski, Rosanne, Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Chen, Xin] NCI Frederick, Basic Res Program, SAIC Frederick, Frederick, MD USA. [Hall, Veronica L.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21701 USA.
    1. Year: 2008
    2. Date: Oct 15
    3. Epub Date: 7/29/2008
  2. Journal: Blood
    1. 112
    2. 8
    3. Pages: 3283-3292
  4. Type of Article: Article
  5. ISSN: 0006-4971
  1. Abstract:

    Interleukin-7 (IL-7), a cytokine produced by stromal cells, is required for thymic development and peripheral homeostasis of most major subsets of T cells. We examined whether regulatory T (Treg) cells also required the IL-7 pathway by analyzing IL-7R alpha(-/-) mice. We observed a striking reduction in cells with the Treg surface phenotype (CD4, CD25, GITR (glucocorticoid-induced tumor necrosis factor [TNF]-like receptor), CD45RB, CD62L, CD103) or intracellular markers (cytotoxic T-lymphocyte associated antigen-4, CTLA-4, and forkhead box transcription factor 3, Foxp3). Foxp3 transcripts were virtually absent in IL-7R alpha(-/-) lymphoid tissues, and no Treg cell suppressive activity could be detected. There are 2 known ligands for IL-7R alpha: IL-7 itself and thymic stromal lymphopoietin (TSLP). Surprisingly, mice deficient in IL-7 or the other chain of the TSLP receptor (TSLPR) developed relatively normal numbers of Treg cells. Combined deletion of IL-7 and TSLP receptor greatly reduced Treg cell development in the thymus but was not required for survival of mature peripheral Treg cells. We conclude that Treg cells, like other T cells, require signals from the IL-7 receptor, but unlike other T cells, do not require IL-7 itself because of at least partially overlapping actions of IL-7 and TSLP for development of Treg cells.

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  2. DOI: 10.1182/blood-2008-02-137414
  3. PMID: 18664628
  4. PMCID: PMC2569178

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