Coexpression of PD-1,2B4,CD160 and KLRG1 on exhausted HCV-specific CD8+ T cells is linked to antigen recognition and T cell differentiation

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-specific cd8+ t cells occurred in concert with a cd127hi phenotype,an early t cell differentiation stage and presence of viral sequence variations within the corresponding epitopes. in sum,these results suggest that tcell exhaustion contributes to the failure of about half of hcv-specific cd8+ t cell responses and that it is determined by a complex interplay of immunological (e.g. t cell differentiation) and virological (e.g. ongoing antigen triggering) factors. © 2010 bengsch et al.