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

H J Hartling; J C Gaardbo; A Ronit; L S Knudsen; H Ullum; Ben Vainer; M R Clausen; K Skogstrand; J Gerstoft; S D Nielsen

doi:10.1111/j.1365-3083.2012.02725.x

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

H J Hartling, J C Gaardbo, A Ronit, L S Knudsen, H Ullum, Ben Vainer, M R Clausen, K Skogstrand, J Gerstoft, S D Nielsen

27 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Scandinavian Journal of Immunology
Volume	76
Issue number	3
Pages (from-to)	294-305
Number of pages	12
ISSN	0300-9475
DOIs	https://doi.org/10.1111/j.1365-3083.2012.02725.x
Publication status	Published - Sept 2012

Keywords

CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Coinfection
Cross-Sectional Studies
Elasticity Imaging Techniques
Female
Fibrosis
Flow Cytometry
HIV Infections
Hepatitis C, Chronic
Humans
Liver
Male
Middle Aged
Phenotype
T-Lymphocytes, Regulatory

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/j.1365-3083.2012.02725.x

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Hartling, H. J., Gaardbo, J. C., Ronit, A., Knudsen, L. S., Ullum, H., Vainer, B., Clausen, M. R., Skogstrand, K., Gerstoft, J., & Nielsen, S. D. (2012). 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. Scandinavian Journal of Immunology, 76(3), 294-305. https://doi.org/10.1111/j.1365-3083.2012.02725.x

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. / Hartling, H J; Gaardbo, J C; Ronit, A et al.

In: Scandinavian Journal of Immunology, Vol. 76, No. 3, 09.2012, p. 294-305.

Research output: Contribution to journal › Journal article › Research › peer-review

Hartling, HJ, Gaardbo, JC, Ronit, A, Knudsen, LS, Ullum, H, Vainer, B, Clausen, MR, Skogstrand, K, Gerstoft, J & Nielsen, SD 2012, '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', Scandinavian Journal of Immunology, vol. 76, no. 3, pp. 294-305. https://doi.org/10.1111/j.1365-3083.2012.02725.x

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title = "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",

abstract = "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.",

keywords = "CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Coinfection, Cross-Sectional Studies, Elasticity Imaging Techniques, Female, Fibrosis, Flow Cytometry, HIV Infections, Hepatitis C, Chronic, Humans, Liver, Male, Middle Aged, Phenotype, T-Lymphocytes, Regulatory",

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doi = "10.1111/j.1365-3083.2012.02725.x",

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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

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

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DO - 10.1111/j.1365-3083.2012.02725.x

M3 - Journal article

C2 - 22671952

SN - 0301-6323

VL - 76

SP - 294

EP - 305

JO - Scandinavian Journal of Immunology, Supplement

JF - Scandinavian Journal of Immunology, Supplement

IS - 3

ER -

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

Abstract

Keywords

UN SDGs

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