CD4⁺ and CD8⁺ regulatory T cells (Tregs) are elevated and display an active phenotype in patients with chronic HCV mono-infection and HIV/HCV co-infection

TY - JOUR

T1 - CD4⁺ and CD8⁺ regulatory T cells (Tregs) are elevated and display an active phenotype in patients with chronic HCV mono-infection and HIV/HCV co-infection

AU - Hartling, H J

AU - Gaardbo, J C

AU - Ronit, A

AU - Knudsen, L S

AU - Ullum, H

AU - Vainer, Ben

AU - Clausen, M R

AU - Skogstrand, K

AU - Gerstoft, J

AU - Nielsen, S D

N1 - © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd.

PY - 2012/9

Y1 - 2012/9

N2 - The aim of this study was to examine regulatory T cells (Tregs) in peripheral blood and liver tissue in patients with chronic hepatitis C virus (HCV) mono-infection and in patients with HIV/HCV co-infection. In a cross-sectional study were included 51 patients with chronic HCV infection, 24 patients with HIV/HCV co-infection and 24 healthy individuals. CD4 + and CD8 + Tregs were determined using flow cytometry. Fibrosis was examined by transient elastography. Inflammation, fibrosis and Tregs were determined in liver biopsies from 12 patients. Increased frequency of CD4 + and CD8 + Tregs was found in HIV/HCV co-infected patients [median: 6.4% (IQR: 5.7-6.9) and 1.0% (0.7-1.2), respectively] compared to HCV mono-infected patients [5.6% (4.2-6.3), P=0.01 and 0.5% (0.3-0.7), P<0.001, respectively]. Furthermore, HCV mono-infected patients had increased frequencies of Tregs compared with healthy controls (P<0.05). However, no associations between the frequency of Tregs and fibrosis were found. Furthermore, characterization of CD4 + Tregs using CD45RA demonstrated a higher frequency of activated Tregs in both HCV mono-infected and HIV/HCV co-infected patients compared with healthy controls. Finally, number of intrahepatic Tregs was associated with both peripheral CD8 + Tregs and intrahepatic inflammation. In conclusion, HCV mono-infected patients and particularly HIV/HCV co-infected patients have increased the frequency of CD4 + and CD8 + Tregs compared with healthy controls. Furthermore, CD4 + Tregs in infected patients displayed an active phenotype. Tregs were not associated with fibrosis, but a positive correlation between intrahepatic Tregs and inflammation was found. Taken together, these results suggest a role for Tregs in the pathogenesis of chronic HCV infection.

AB - The aim of this study was to examine regulatory T cells (Tregs) in peripheral blood and liver tissue in patients with chronic hepatitis C virus (HCV) mono-infection and in patients with HIV/HCV co-infection. In a cross-sectional study were included 51 patients with chronic HCV infection, 24 patients with HIV/HCV co-infection and 24 healthy individuals. CD4 + and CD8 + Tregs were determined using flow cytometry. Fibrosis was examined by transient elastography. Inflammation, fibrosis and Tregs were determined in liver biopsies from 12 patients. Increased frequency of CD4 + and CD8 + Tregs was found in HIV/HCV co-infected patients [median: 6.4% (IQR: 5.7-6.9) and 1.0% (0.7-1.2), respectively] compared to HCV mono-infected patients [5.6% (4.2-6.3), P=0.01 and 0.5% (0.3-0.7), P<0.001, respectively]. Furthermore, HCV mono-infected patients had increased frequencies of Tregs compared with healthy controls (P<0.05). However, no associations between the frequency of Tregs and fibrosis were found. Furthermore, characterization of CD4 + Tregs using CD45RA demonstrated a higher frequency of activated Tregs in both HCV mono-infected and HIV/HCV co-infected patients compared with healthy controls. Finally, number of intrahepatic Tregs was associated with both peripheral CD8 + Tregs and intrahepatic inflammation. In conclusion, HCV mono-infected patients and particularly HIV/HCV co-infected patients have increased the frequency of CD4 + and CD8 + Tregs compared with healthy controls. Furthermore, CD4 + Tregs in infected patients displayed an active phenotype. Tregs were not associated with fibrosis, but a positive correlation between intrahepatic Tregs and inflammation was found. Taken together, these results suggest a role for Tregs in the pathogenesis of chronic HCV infection.

KW - CD4-Positive T-Lymphocytes

KW - CD8-Positive T-Lymphocytes

KW - Coinfection

KW - Cross-Sectional Studies

KW - Elasticity Imaging Techniques

KW - Female

KW - Fibrosis

KW - Flow Cytometry

KW - HIV Infections

KW - Hepatitis C, Chronic

KW - Humans

KW - Liver

KW - Male

KW - Middle Aged

KW - Phenotype

KW - T-Lymphocytes, Regulatory

U2 - 10.1111/j.1365-3083.2012.02725.x

DO - 10.1111/j.1365-3083.2012.02725.x

M3 - Journal article

C2 - 22671952

SN - 0300-9475

VL - 76

SP - 294

EP - 305

JO - Scandinavian Journal of Immunology

JF - Scandinavian Journal of Immunology

IS - 3

ER -