coexpression of pd-1, 2b4, cd160 and klrg1 on exhausted hcv-specific cd8+ t cells is linked to antigen recognition and t cell differentiationcoexpression pd-1,2 b4,cd160和klrg1疲惫丙肝病毒的cd8 + t细胞与抗原识别和t细胞分化.pdf

Coexpression of PD-1, 2B4, CD160 and KLRG1 on Exhausted HCV-Specific CD8+ T Cells Is Linked to Antigen Recognition and T Cell Differentiation 1,2,3. 1,2,3. 4 ¨ 4 1 1 Bertram Bengsch , Bianca Seigel , Marianne Ruhl , Jorg Timm , Martin Kuntz , Hubert E. Blum , 5 1 Hanspeter Pircher , Robert Thimme * 1 Department of Medicine II, University of Freiburg, Freiburg, Germany, 2 Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany, 3 Faculty of Biology, University of Freiburg, Freiburg, Germany, 4 Department of Virology, University of Essen, Essen, Germany, 5 Department of Immunology, University of Freiburg, Freiburg, Germany Abstract Exhausted CD8+ T cell responses during chronic viral infections are defined by a complex expression pattern of inhibitory receptors. However, very little information is currently available about the coexpression patterns of these receptors on human virus-specific CD8+ T cells and their correlation with antiviral functions, T cell differentiation and antigen recognition. We addressed these important aspects in a cohort of 38 chronically HCV infected patients and found a coexpression of inhibitory receptors such as 2B4, CD160 and KLRG1 in association with PD-1 in about half of the HCV-specific CD8+ T cell responses. Importantly, this exhaustive phenotype was associated with low and intermediate levels of CD127 expression, an impaired proliferative capacity, an intermediate T cell differentiation stage and absence of sequence variations within the corresponding epitopes, indicating ongoing antigen triggering. In contrast, a low expression of inhibitory receptors by the remaining HCV-spe