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 (TGF-β) controls the development of TCRαβ+CD8αα+ IELs. Mice with either a null mutation in the gene encoding TGF-β1 or T cell–specific deletion of TGF-β receptor I lacked TCRαβ+CD8αα+ IELs, whereas mice with transgenic overexpression of TGF-β1 had a larger population of TCRαβ+CD8αα+ IELs. We observed defective development of the TCRαβ+CD8αα+ IEL thymic precursors (CD4−CD8−TCRαβ+CD5+) in the absence of TGF-β. In addition, we found that TGF-β signaling induced CD8α expression in TCRαβ+CD8αα+ IEL thymic precursors and induced and maintained CD8α expression in peripheral populations of T cells. Our data demonstrate a previously unrecognized role for TGF-β in the development of TCRαβ+CD8αα+ IELs and the expression of CD8α in T cells.
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We thank G. McGrady and S. Wahl (National Institute of Dental and Craniofacial Research, National Institutes of Health) for Tgfb1−/− mice, and E. Stregevsky and J. Simone for technical assistance. Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research and National Cancer Institute, Center for Cancer Research.
The authors declare no competing financial interests.
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Konkel, J., Maruyama, T., Carpenter, A. et al. Control of the development of CD8αα+ intestinal intraepithelial lymphocytes by TGF-β. Nat Immunol 12, 312–319 (2011). https://doi.org/10.1038/ni.1997
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