Imprint of unconventional T-cell response in acute hepatitis C persists despite successful early antiviral treatment
Standard
Imprint of unconventional T-cell response in acute hepatitis C persists despite successful early antiviral treatment. / Du, Yanqin; Khera, Tanvi; Strunz, Benedikt; Deterding, Katja; Todt, Daniel; Woller, Norman; Engelskircher, Sophie Anna; Hardtke, Svenja; Port, Kerstin; Ponzetta, Andrea; Steinmann, Eike; Cornberg, Markus; Hengst, Julia; Björkström, Niklas K; Wedemeyer, Heiner; HepNet Acute HCV IV Study Group.
In: EUR J IMMUNOL, Vol. 52, No. 3, 03.2022, p. 472-483.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Imprint of unconventional T-cell response in acute hepatitis C persists despite successful early antiviral treatment
AU - Du, Yanqin
AU - Khera, Tanvi
AU - Strunz, Benedikt
AU - Deterding, Katja
AU - Todt, Daniel
AU - Woller, Norman
AU - Engelskircher, Sophie Anna
AU - Hardtke, Svenja
AU - Port, Kerstin
AU - Ponzetta, Andrea
AU - Steinmann, Eike
AU - Cornberg, Markus
AU - Hengst, Julia
AU - Björkström, Niklas K
AU - Wedemeyer, Heiner
AU - HepNet Acute HCV IV Study Group
N1 - © 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
PY - 2022/3
Y1 - 2022/3
N2 - Unconventional T cells (UTCs) are a heterogeneous group of T cells that typically exhibit rapid responses toward 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. Furthermore, MAIT cell functionality was systematically studied. 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, which subsequently normalized during the treatment. In addition, DNT cell activation was specifically associated with liver inflammation and inflammatory cytokines. 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.
AB - Unconventional T cells (UTCs) are a heterogeneous group of T cells that typically exhibit rapid responses toward 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. Furthermore, MAIT cell functionality was systematically studied. 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, which subsequently normalized during the treatment. In addition, DNT cell activation was specifically associated with liver inflammation and inflammatory cytokines. 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.
U2 - 10.1002/eji.202149457
DO - 10.1002/eji.202149457
M3 - SCORING: Journal article
C2 - 34843107
VL - 52
SP - 472
EP - 483
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 3
ER -
