title: TGF-β downregulates KLRG1 expression in mouse and human CD8(+) T cells.
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.
authors.affiliation: Institute for Immunology, University Medical Center Freiburg, Freiburg, Germany.|Faculty of Biology, Albert-Ludwigs-University of Freiburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schwartzkopff
authors.affiliation: Institute for Immunology, University Medical Center Freiburg, Freiburg, Germany.|Faculty of Biology, Albert-Ludwigs-University of Freiburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Woyciechowski
authors.affiliation: Institute for Immunology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Aichele
authors.affiliation: Faculty of Biology, Albert-Ludwigs-University of Freiburg, Germany.|Department of Medicine II, University Medical Center Freiburg, Freiburg, Germany.|Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University of Freiburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Flecken
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Nu
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Medicine II, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.affiliation: Institute for Immunology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Pircher
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015820:Cadherins / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D039001:Integrin alpha Chains; C113413:KLRG1 protein, human; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C091367:alpha E integrins
keywords: E-cadherin. CD8+ T cell; Killer cell lectin-like receptor G1; TGF-β; αE (CD103)