TGF-β downregulates KLRG1 expression in mouse and human CD8(+) T cells

Eur J Immunol. 2015 Aug;45(8):2212-7. doi: 10.1002/eji.201545634. Epub 2015 Jun 15.


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.

Keywords: E-cadherin. CD8+ T cell; Killer cell lectin-like receptor G1; TGF-β; αE (CD103).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cadherins / genetics
  • Cadherins / immunology
  • Cell Differentiation / immunology*
  • Down-Regulation / immunology*
  • Humans
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / immunology
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Mice
  • Mice, Transgenic
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Trans-Activators / genetics
  • Trans-Activators / immunology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology*


  • Antigens, CD
  • Cadherins
  • Integrin alpha Chains
  • KLRG1 protein, human
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, Immunologic
  • Trans-Activators
  • Transforming Growth Factor beta
  • alpha E integrins