Nonreversible MAIT cell-dysfunction in chronic hepatitis C virus infection despite successful interferon-free therapy.
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.
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.|Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Julia
J
Hengst
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Benedikt
B
Strunz
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Katja
K
Deterding
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Hans-Gustaf
HG
Ljunggren
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.|Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore.
Edwin
E
Leeansyah
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Center for Infection Research, partner site Hannover-Braunschweig, Germany.
Michael P
MP
Manns
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Center for Infection Research, partner site Hannover-Braunschweig, Germany.
Markus
M
Cornberg
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Johan K
JK
Sandberg
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Center for Infection Research, partner site Hannover-Braunschweig, Germany.
Heiner
H
Wedemeyer
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. niklas.bjorkstrom@ki.se.
Niklas K
NK
Björkström
D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D016022:Case-Control Studies; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D015778:Minor Histocompatibility Antigens / Q000378:metabolism; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D015415:Biomarkers; D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D014157:Transcription Factors
Chronic infection; HCV; Immune exhaustion; Interferon-free therapy; MAIT cells