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J. Virol. doi:10.1128/JVI.01354-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Analysis of CD127 and KLRG1 expression on HCV specific CD8+ T cells reveals the existence of different memory T cell subsets in the peripheral blood and liver

Department of Medicine II and Department of Immunology, Institute of Medical Microbiology, University of Freiburg, Germany

^* To whom correspondence should be addressed. Email: thimme{at}med1.ukl.uni-freiburg.de.

	Abstract

The differentiation and functional status of virus-specific CD8+ T cells is significantly influenced by specific and ongoing antigen recognition. Importantly, the expression profile of the IL-7 receptor alpha chain (CD127) and the killer cell lectin-like receptor G1 (KLRG1) has been shown to be differentially influenced by repetitive T cell receptor (TCR) interactions. Indeed, antigen-specific CD8+ T cells targeting persistent viruses (e.g., HIV, EBV) have been shown to have a low CD127 and a high KLRG1 expression while CD8+ T cells targeting resolved viral antigens (e.g., FLU) typically display a high CD127 and a low KLRG1 expression. Here, we analyzed the surface phenotype and function of HCV-specific CD8+ T cells. Surprisingly, despite viral persistence we found that a large fraction of peripheral HCV-specific CD8+ T cells were CD127+ and KLRG1- and had a good proliferative capacity, thus resembling memory cells that usually develop following acute resolving infection. Intrahepatic virus-specific CD8+ T cells displayed a significantly reduced expression of CD127 but similar levels of KLRG1 expression as compared to the peripheral blood. These results extend previous studies that demonstrated a memory (CCR7+) and early-differentiated phenotype of HCV-specific CD8+ T cells and suggest that insufficient stimulation of virus-specific CD8+ T cells by viral antigen may be responsible for this alteration in HCV-specific CD8+ T cell differentiation during chronic HCV infection.

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