PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion |
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Authors: | Urbani Simona Amadei Barbara Tola Daniela Massari Marco Schivazappa Simona Missale Gabriele Ferrari Carlo |
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Institution: | Laboratorio Immunopatologia Virale, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43100 Parma, Italy. |
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Abstract: | Hepatitis C virus (HCV)-specific CD8 cell exhaustion may represent a mechanism of HCV persistence. The inhibitory receptor PD-1 has been reported to be up-regulated in exhausted CD8 cells. Therefore, we studied PD-1 expression longitudinally during acute HCV infection. Most HCV-specific CD8 cells expressed PD-1 at the time of acute illness, irrespective of the final outcome. PD-1 expression declined with the acquisition of a memory phenotype and recovery of an efficient CD8 cell function in resolving HCV infections, whereas high levels were maintained when HCV persisted and HCV-specific CD8 cells remained dysfunctional. Blocking PD-1/PDL-1 interaction with an anti-PDL-1 antibody improved the capacity of expansion of virus-specific CD8 cells. |
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