Control of the development of CD8αα+ intestinal intraepithelial lymphocytes by TGF-β

Joanne E. Konkel, Takashi Maruyama, Andrea C. Carpenter, Yumei Xiong, Brian F. Zamarron, Bradford E. Hall, Ashok B. Kulkarni, Pin Zhang, Remy Bosselut, Wanjun Chen

    Research output: Contribution to journalArticlepeer-review

    92 Citations (Scopus)

    Abstract

    The molecular mechanisms that direct the development of TCRαβ+ CD8αα+ intestinal intraepithelial lymphocytes (IELs) are not thoroughly understood. Here we show that transforming growth factor-β 2 (TGF-β 2) controls the development of TCRβ αβ+ CD8β αβ α+ IELs. Mice with either a null mutation in the gene encoding TGF-β 21 or T cell-specific deletion of TGF-β receptor I lacked TCRβ αβ+ CD8β αβ α+ IELs, whereas mice with transgenic overexpression of TGF-β 21 had a larger population of TCRβ αβ+ CD8β αβ α+ IELs. We observed defective development of the TCRβ αβ+ CD8β αβ α+ IEL thymic precursors (CD4 -CD8 -TCRβ αβ+ CD5+) in the absence of TGF-β 2. In addition, we found that TGF-β 2 signaling induced CD8β α expression in TCRβ αβ+ CD8β αβ α+ IEL thymic precursors and induced and maintained CD8β ± expression in peripheral populations of T cells. Our data demonstrate a previously unrecognized role for TGF-β 2 in the development of TCRβ αβ+ CD8β αβ +IELs and the expression of CD8β α in T cells.

    Original languageEnglish
    Pages (from-to)312-320
    Number of pages9
    JournalNature Immunology
    Volume12
    Issue number4
    DOIs
    Publication statusPublished - 2011 Apr

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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