Imprint of unconventional T cell response in acute hepatitis C persists despite successful early antiviral treatment

Unconventional T cells (UTCs) are a heterogenous group of T cells that typically exhibit rapid responses towards specific antigens from pathogens. Chronic hepatitis C virus (HCV) infection causes dysfunction of several subsets of UTCs. This altered phenotype and function of UTCs can persist over time even after direct acting antiviral (DAA) mediated clearance of chronic HCV. However, it is less clear if and how UTCs respond in acute, symptomatic HCV infection, a rare clinical condition, and if rapid DAA treatment of such patients reverses the caused perturbations within UTCs. Here, we comprehensively analyzed the phenotype and reinvigoration capacity of three major UTC populations, mucosal associated invariant T (MAIT) cells, γδ T cells, and CD4 and CD8 double-negative αβ T cells (DNT cells) before, during, and after DAA-mediated clearance of acute symptomatic HCV infection. Among that, MAIT cell functionality was also systematically analyzed. We observed a reduced frequency of MAIT cells. However, remaining cells presented with a near-to-normal phenotype in acute infection, which contrasted with a significant dysfunction upon stimulation that was not restored after viral clearance. Notably, DNT and γδ T cells displayed a strong activation ex-vivo in acute HCV infection, that subsequently normalized during the course of treatment. In addition, DNT cell activation was specifically associated to liver inflammation. Altogether, these data provide evidence that UTCs respond in a cell type-specific manner during symptomatic HCV infection. However, even if early treatment is initiated, long-lasting imprints within UTCs remain over time.

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Artikel online veröffentlicht:
26. Januar 2022