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

JE Konkel, T Maruyama, AC Carpenter, Y Xiong… - Nature …, 2011 - nature.com
JE Konkel, T Maruyama, AC Carpenter, Y Xiong, BF Zamarron, BE Hall, AB Kulkarni
Nature immunology, 2011nature.com
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 …
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 (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 (CD4CD8TCRαβ+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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