loading page

Influence of HLA-C environment on the spontaneous clearance of hepatitis C in European HIV-HCV co-infected individuals
  • +9
  • Nolwenn Legrand,
  • Gaëlle David,
  • Audrey Rodallec,
  • Aurélie Gaultier,
  • Dominique Salmon,
  • Anne Cesbron,
  • Linda Wittkop,
  • François Raffi,
  • Ketevan Gendzekhadze,
  • Christelle Retiere,
  • Clotilde Allavena,
  • Katia Gagne
Nolwenn Legrand
EFS
Author Profile
Gaëlle David
Etablissement Français du Sang
Author Profile
Audrey Rodallec
CHU Hotel Dieu
Author Profile
Aurélie Gaultier
CHU Hotel Dieu
Author Profile
Dominique Salmon
APHP
Author Profile
Anne Cesbron
EFS
Author Profile
Linda Wittkop
CHU
Author Profile
François Raffi
CHU Hotel Dieu
Author Profile
Ketevan Gendzekhadze
City of Hope medican center
Author Profile
Christelle Retiere
Etablissement Fraçais du Sang
Author Profile
Clotilde Allavena
CHU Hotel Dieu
Author Profile
Katia Gagne
EFS
Author Profile

Abstract

Natural Killer (NK) cell functions are regulated by diverse inhibitory and activating receptors including Killer cell Immunoglobulin-like receptors (KIR) which interact with HLA class I molecules. Some KIR/HLA genetic combinations were reported associated with spontaneous clearance (SC) of hepatitis C virus (HCV) but with discordant results, possibly reflecting KIR and/or HLA gene polymorphism according to populations. KIR/HLA genetic combinations associated with both an exhaustive NK and T cell repertoire were investigated in a cohort of HIV-HCV co-infected individuals with either SC (n=68) or chronic infection (CI, n=163) compared to uninfected blood donors (Ctrl, n=100). Multivariate analysis showed that the HLA C2C2 environment was associated with SC only in European HIV-HCV co-infected individuals (OR=4.30[1.57-12.25], p=0.005). KIR2D+ NK cell repertoire and potential of degranulation of KIR2DL1/S1+ NK cells were similar in SC European cohort compared to uninfected individuals. In contrast, decreased frequencies of KIR2DS1+ and KIR2DL2+ NK cells were detected in CI group of Europeans compared to SC and a decreased frequency of KIR2DL1/S1+ NK cells compared to controls. On the T cell side, higher frequencies of DNAM-1+ and CD57+ T cells were observed in SC in comparison to controls. Interestingly, SC subjects emphasized increased frequencies of KIR2DL2/L3/S2+ T cells compared to CI subjects. Our study underlines that the C2 environment may activate efficient KIR2DL1+ NK cells in viral context and maintain KIR2DL2/L3/S2+ mature T cell response in the absence of KIR2DL2 engagement with its cognate ligands in SC group of HCV-HIV co-infected European patients.

Peer review status:UNDER REVIEW

05 Aug 2020Submitted to Clinical & Experimental Immunology
05 Aug 2020Assigned to Editor
05 Aug 2020Submission Checks Completed
21 Aug 2020Reviewer(s) Assigned