Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 46, Issue 9, Pages 2204-2210Publisher
WILEY
DOI: 10.1002/eji.201646447
Keywords
Chronic infection; HCV; Immune exhaustion; Interferon-free therapy; MAIT cells
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Funding
- Novo Nordisk Fonden [NNF14OC0009347] Funding Source: researchfish
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Immune exhaustion is a hallmark of chronic viral infections. However, pathogen eradication can result in reinvigorated immune responses. Indeed, this was recently suggested for antigen-specific CD8(+) T cells and NK cells in HCV-infected patients receiving an interferon-free treatment regimen. Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved innate-like effector T cells. Here, we show that MAIT cells are severely diminished in frequency in chronic HCV-infection, and in this regard the most affected immune cell type in peripheral blood of humans with this disease. Residual MAIT cells show an activated phenotype with high expression of granzyme B, HLA-DR, PD-1, and CD69 as well as altered transcription factor expression and suppressed responsiveness to MR1-dependent antigen stimulation. In contrast to other immune cells, MAIT cells are not reinvigorated after successful HCV-clearance using interferon-free therapy. The present results hence demonstrate persistent immune cell-dysfunction in humans despite successful elimination of a chronic pathogen.
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