Polyfunctional type-1,-2,and -17 CD8+ T cell responses to apoptotic self-antigens correlate with the chronic evolution of hepatitis C virus infection

Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of cd8+ t cell responses in various infectious diseases. we found that the emergence of a large population of autoreactive cd8+ t effector cells specific for apoptotic t cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis c virus infection. importantly,they endow mixed polyfunctional type-1,type-2 and type-17 responses and correlate with the chronic progression of infection. this evolution is related to the selection of autoreactive cd8+ t cells with higher t cell receptor avidity,whereas those with lower avidity undergo prompt contraction in patients who clear infection. these findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive cd8+ t cells producing a broad array of cytokines (ifn-γ,il-17,il-4,il-2...) and the progression toward chronic disease in a human model of acute infection. © 2012 franceschini et al.