PMID- 33314121
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20221005
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 204
IP  - 1
DP  - 2021 Apr
TI  - Influence of HLA-C environment on the spontaneous clearance of hepatitis C in 
      European HIV-HCV co-infected individuals.
PG  - 107-124
LID - 10.1111/cei.13562 [doi]
AB  - Natural killer (NK) cell functions are regulated by diverse inhibitory and 
      activating receptors, including killer cell immunoglobulin-like receptors (KIR), 
      which interact with human leukocyte antigen (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 
      [controls (Ctrl), n = 100]. Multivariate analysis showed that the HLA C2C2 
      environment was associated with SC only in European HIV-HCV co-infected 
      individuals [odds ratio (OR) = 4.30, 95% confidence interval = 1.57-12.25, 
      P = 0.005]. KIR2D(+) NK cell repertoire and potential of degranulation of 
      KIR2DL1/S1(+) NK cells were similar in the SC European cohort compared to 
      uninfected individuals. In contrast, decreased frequencies of KIR2DS1(+) and 
      KIR2DL2(+) NK cells were detected in the CI group of Europeans compared to SC and 
      a decreased frequency of KIR2DL1/S1(+) NK cells compared to controls. Regarding T 
      cells, higher frequencies of DNAX accessory molecule-1 (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 a viral context and maintain a 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.
CI  - (c) 2021 British Society for Immunology.
FAU - Legrand, N
AU  - Legrand N
AD  - Etablissement Francais du Sang (EFS), Nantes, France.
AD  - Universite de Nantes, INSERM U1232 CNRS, CRCINA, Nantes, France.
FAU - David, G
AU  - David G
AD  - Etablissement Francais du Sang (EFS), Nantes, France.
AD  - Universite de Nantes, INSERM U1232 CNRS, CRCINA, Nantes, France.
FAU - Rodallec, A
AU  - Rodallec A
AD  - Department of Virology, CHU Nantes Hotel Dieu, Nantes, France.
FAU - Gaultier, A
AU  - Gaultier A
AD  - Department of Biostatistics, CHU Hotel Dieu, Nantes, France.
FAU - Salmon, D
AU  - Salmon D
AD  - AP-HP Department of Infectious Diseases, Universite Paris Descartes, Paris, 
      France.
FAU - Cesbron, A
AU  - Cesbron A
AD  - EFS, HLA Laboratory, Nantes, France.
FAU - Wittkop, L
AU  - Wittkop L
AD  - INSERM UMR1219, Universite de Bordeaux ISPED, Bordeaux, France.
FAU - Raffi, F
AU  - Raffi F
AD  - Department of Infectious Diseases, Nantes, France.
FAU - Gendzekhadze, K
AU  - Gendzekhadze K
AD  - Division of Hematology and Bone Marrow Transplantation, Duarte, CA, USA.
FAU - Retiere, C
AU  - Retiere C
AD  - Etablissement Francais du Sang (EFS), Nantes, France.
AD  - Universite de Nantes, INSERM U1232 CNRS, CRCINA, Nantes, France.
AD  - LabEx IGO, Nantes, France.
FAU - Allavena, C
AU  - Allavena C
AD  - Department of Infectious Diseases, Nantes, France.
FAU - Gagne, K
AU  - Gagne K
AUID- ORCID: 0000-0002-4467-5961
AD  - Etablissement Francais du Sang (EFS), Nantes, France.
AD  - Universite de Nantes, INSERM U1232 CNRS, CRCINA, Nantes, France.
AD  - LabEx IGO, Nantes, France.
AD  - LabEx Transplantex, Universite de Strasbourg, Strasbourg, France.
LA  - eng
GR  - VX-950HHC001/Janssen Research and Development/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210202
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (HLA-C Antigens)
RN  - 0 (KIR2DL1 protein, human)
RN  - 0 (KIR2DL2 protein, human)
RN  - 0 (KIR2DS1 protein, human)
RN  - 0 (Receptors, KIR)
RN  - 0 (Receptors, KIR2DL1)
RN  - 0 (Receptors, KIR2DL2)
RN  - 0 (Receptors, KIR2DL3)
SB  - IM
MH  - Adult
MH  - Cells, Cultured
MH  - Coinfection/*immunology
MH  - Female
MH  - Flow Cytometry/methods
MH  - France
MH  - Genotype
MH  - HIV Infections/*immunology
MH  - HLA-C Antigens/genetics/*immunology
MH  - Hepatitis C/*immunology
MH  - Humans
MH  - Killer Cells, Natural/immunology/metabolism
MH  - Male
MH  - Middle Aged
MH  - Receptors, KIR/genetics/immunology
MH  - Receptors, KIR2DL1/genetics/immunology
MH  - Receptors, KIR2DL2/genetics/immunology
MH  - Receptors, KIR2DL3/genetics/immunology
MH  - Remission, Spontaneous
MH  - T-Lymphocyte Subsets/immunology/metabolism
PMC - PMC7944354
OTO - NOTNLM
OT  - HLA
OT  - KIR
OT  - co-infection
OT  - hepatitis C
OT  - spontaneous clearance
COIS- The authors declare that they have nothing to disclose regarding funding or 
      conflicts of interest with respect to this manuscript. All the authors approved 
      the manuscript.
EDAT- 2020/12/15 06:00
MHDA- 2021/09/28 06:00
PMCR- 2022/04/01
CRDT- 2020/12/14 11:06
PHST- 2020/08/05 00:00 [received]
PHST- 2020/12/07 00:00 [revised]
PHST- 2020/12/07 00:00 [accepted]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2020/12/14 11:06 [entrez]
PHST- 2022/04/01 00:00 [pmc-release]
AID - CEI13562 [pii]
AID - 10.1111/cei.13562 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2021 Apr;204(1):107-124. doi: 10.1111/cei.13562. Epub 2021 Feb 
      2.