TY - JOUR
T1 - TGF-β downregulates KLRG1 expression in mouse and human CD8+ T cells
AU - Schwartzkopff, Sabrina
AU - Woyciechowski, Sandra
AU - Aichele, Ulrike
AU - Flecken, Tobias
AU - Zhang, Nu
AU - Thimme, Robert
AU - Pircher, Hanspeter
N1 - Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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.
KW - E-cadherin. CD8 T cell
KW - Killer cell lectin-like receptor G1
KW - TGF-β
KW - α (CD103)
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U2 - 10.1002/eji.201545634
DO - 10.1002/eji.201545634
M3 - Article
C2 - 26014037
AN - SCOPUS:84938953069
SN - 0014-2980
VL - 45
SP - 2212
EP - 2217
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 8
ER -