TGF‐β downregulates KLRG1 expression in mouse and human CD8+ T cells |
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Authors: | Sabrina Schwartzkopff Sandra Woyciechowski Ulrike Aichele Tobias Flecken Nu Zhang Robert Thimme Hanspeter Pircher |
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Affiliation: | 1. Institute for Immunology, University Medical Center Freiburg, Freiburg, Germany;2. Faculty of Biology, Albert‐Ludwigs‐University of Freiburg, Germany;3. Department of Medicine II, University Medical Center Freiburg, Freiburg, Germany;4. Spemann Graduate School of Biology and Medicine (SGBM), Albert‐Ludwigs‐University of Freiburg, Germany;5. Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA |
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Abstract: | The inhibitory receptor killer cell lectin‐like receptor G1 (KLRG1) and the integrin αE (CD103) are expressed by CD8+ T cells and both are specific for E‐cadherin. However, KLRG1 ligation by E‐cadherin inhibits effector T‐cell function, whereas binding of CD103 to E‐cadherin enhances cell–cell interaction and promotes target cell lysis. Here, we demonstrate that KLRG1 and CD103 expression in CD8+ T cells from untreated and virus‐infected mice are mutually exclusive. Inverse correlation of KLRG1 and CD103 expression was also found in human CD8+ T cells‐infiltrating hepatocellular carcinomas. As TGF‐β is known to induce CD103 expression in CD8+ T cells, we examined whether this cytokine also regulates KLRG1 expression. Indeed, our data further reveal that TGF‐β signaling in mouse as well as in human CD8+ T cells downregulates KLRG1 expression. This finding provides a rationale for the reciprocal expression of KLRG1 and CD103 in different CD8+ T‐cell subsets. In addition, it points to the limitation of KLRG1 as a marker for terminally differentiated CD8+ T cells if lymphocytes from tissues expressing high levels of TGF‐β are analyzed. |
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Keywords: | Killer cell lectin‐like receptor G1 α E (CD103) E‐cadherin. CD8+ T cell TGF‐β |
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