Vδ1T Lymphocytes Expressing a Th1 Phenotype Are the Major γδ T Cell Subset Infiltrating the Liver of HCV-infected Persons

Chiara Agrati, Giampiero D'Offizi, Pasquale Narciso, Sergio Abrignani, Giuseppe Ippolito, Vittorio Colizzi, Fabrizio Poccia

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: Hepatitis C infection induces an acute and chronic liver inflammation that may lead to cirrhosis, liver failure, or hepatocarcinoma. Since the role of αβ T lymphocytes in hepatitis C virus (HCV) immunopathology has been analyzed extensively, we investigated the distribution and functional activation of γδ T cell subsets in chronically HCV-infected patients. Materials and Methods: Blood samples and liver biopsies from 35 patients with compensated chronic HCV infection were compared in terms of T cell subset distribution, expression of activation markers, γδ T cell receptor (TCR) repertoire, and pattern of cytokine production. Moreover, we analyzed whether these immunological parameters were associated with other clinical observations (plasma viremia, ALT levels, Ishak index). Results: Differing from peripheral blood distribution, a specific compartmentalization of Vδ1 T cells (p <0.001) was observed in the liver of HCV patients. These cells rep- resented a relevant fraction of intrahepatic T lymphocytes (1.8-8.7%) and expressed the memory/effector phenotype (CD62-L CD45-RO +CD95 +). This phenotype was consistent with selective homing upon antigen recognition. Mitogenic stimulation of Vδ1 + T lymphocytes recruited in the liver revealed the T helper cell type 1 (Th1) pattern of cytokine secretion. Interestingly, the frequency of interferon-γ (IFN-γ)-producing Vδ1 T cells was associated with an higher degree of liver necroinflammation, measured by the Ishak index. Finally, the T-cell repertoire analysis revealed the absence of Vγ selection in the TCR repertoire of intrahepatic Vγ1 T cells. Conclusions: γδ T cell distribution in the peripheral blood differs from the Vδ1 T cell subset because it is policlonally activated and recruited in the liver of chronic HCV-infected patients. During HCV-infection, this T cell subset may release Th1 cytokines and contribute to the necroinflammatory liver disease.

Original languageEnglish
Pages (from-to)11-19
Number of pages9
JournalMolecular medicine (Cambridge, Mass.)
Volume7
Issue number1
Publication statusPublished - 2001

Fingerprint

T-Lymphocyte Subsets
Hepacivirus
Lymphocytes
T-Lymphocytes
Phenotype
Liver
Chronic Hepatitis C
Virus Diseases
Cytokines
T-Cell Antigen Receptor
Th1 Cells
Viremia
Liver Failure
Hepatitis C
Interferons
Liver Diseases
Fibrosis
Inflammation
Biopsy
Antigens

ASJC Scopus subject areas

  • Genetics

Cite this

Vδ1T Lymphocytes Expressing a Th1 Phenotype Are the Major γδ T Cell Subset Infiltrating the Liver of HCV-infected Persons. / Agrati, Chiara; D&apos;Offizi, Giampiero; Narciso, Pasquale; Abrignani, Sergio; Ippolito, Giuseppe; Colizzi, Vittorio; Poccia, Fabrizio.

In: Molecular medicine (Cambridge, Mass.), Vol. 7, No. 1, 2001, p. 11-19.

Research output: Contribution to journalArticle

@article{72c4d04cd7114e09be9bb097696d0d75,
title = "Vδ1T Lymphocytes Expressing a Th1 Phenotype Are the Major γδ T Cell Subset Infiltrating the Liver of HCV-infected Persons",
abstract = "Background: Hepatitis C infection induces an acute and chronic liver inflammation that may lead to cirrhosis, liver failure, or hepatocarcinoma. Since the role of αβ T lymphocytes in hepatitis C virus (HCV) immunopathology has been analyzed extensively, we investigated the distribution and functional activation of γδ T cell subsets in chronically HCV-infected patients. Materials and Methods: Blood samples and liver biopsies from 35 patients with compensated chronic HCV infection were compared in terms of T cell subset distribution, expression of activation markers, γδ T cell receptor (TCR) repertoire, and pattern of cytokine production. Moreover, we analyzed whether these immunological parameters were associated with other clinical observations (plasma viremia, ALT levels, Ishak index). Results: Differing from peripheral blood distribution, a specific compartmentalization of Vδ1 T cells (p <0.001) was observed in the liver of HCV patients. These cells rep- resented a relevant fraction of intrahepatic T lymphocytes (1.8-8.7{\%}) and expressed the memory/effector phenotype (CD62-L CD45-RO +CD95 +). This phenotype was consistent with selective homing upon antigen recognition. Mitogenic stimulation of Vδ1 + T lymphocytes recruited in the liver revealed the T helper cell type 1 (Th1) pattern of cytokine secretion. Interestingly, the frequency of interferon-γ (IFN-γ)-producing Vδ1 T cells was associated with an higher degree of liver necroinflammation, measured by the Ishak index. Finally, the T-cell repertoire analysis revealed the absence of Vγ selection in the TCR repertoire of intrahepatic Vγ1 T cells. Conclusions: γδ T cell distribution in the peripheral blood differs from the Vδ1 T cell subset because it is policlonally activated and recruited in the liver of chronic HCV-infected patients. During HCV-infection, this T cell subset may release Th1 cytokines and contribute to the necroinflammatory liver disease.",
author = "Chiara Agrati and Giampiero D&apos;Offizi and Pasquale Narciso and Sergio Abrignani and Giuseppe Ippolito and Vittorio Colizzi and Fabrizio Poccia",
year = "2001",
language = "English",
volume = "7",
pages = "11--19",
journal = "Molecular Medicine",
issn = "1076-1551",
publisher = "Feinstein Institute for Medical Research",
number = "1",

}

TY - JOUR

T1 - Vδ1T Lymphocytes Expressing a Th1 Phenotype Are the Major γδ T Cell Subset Infiltrating the Liver of HCV-infected Persons

AU - Agrati, Chiara

AU - D&apos;Offizi, Giampiero

AU - Narciso, Pasquale

AU - Abrignani, Sergio

AU - Ippolito, Giuseppe

AU - Colizzi, Vittorio

AU - Poccia, Fabrizio

PY - 2001

Y1 - 2001

N2 - Background: Hepatitis C infection induces an acute and chronic liver inflammation that may lead to cirrhosis, liver failure, or hepatocarcinoma. Since the role of αβ T lymphocytes in hepatitis C virus (HCV) immunopathology has been analyzed extensively, we investigated the distribution and functional activation of γδ T cell subsets in chronically HCV-infected patients. Materials and Methods: Blood samples and liver biopsies from 35 patients with compensated chronic HCV infection were compared in terms of T cell subset distribution, expression of activation markers, γδ T cell receptor (TCR) repertoire, and pattern of cytokine production. Moreover, we analyzed whether these immunological parameters were associated with other clinical observations (plasma viremia, ALT levels, Ishak index). Results: Differing from peripheral blood distribution, a specific compartmentalization of Vδ1 T cells (p <0.001) was observed in the liver of HCV patients. These cells rep- resented a relevant fraction of intrahepatic T lymphocytes (1.8-8.7%) and expressed the memory/effector phenotype (CD62-L CD45-RO +CD95 +). This phenotype was consistent with selective homing upon antigen recognition. Mitogenic stimulation of Vδ1 + T lymphocytes recruited in the liver revealed the T helper cell type 1 (Th1) pattern of cytokine secretion. Interestingly, the frequency of interferon-γ (IFN-γ)-producing Vδ1 T cells was associated with an higher degree of liver necroinflammation, measured by the Ishak index. Finally, the T-cell repertoire analysis revealed the absence of Vγ selection in the TCR repertoire of intrahepatic Vγ1 T cells. Conclusions: γδ T cell distribution in the peripheral blood differs from the Vδ1 T cell subset because it is policlonally activated and recruited in the liver of chronic HCV-infected patients. During HCV-infection, this T cell subset may release Th1 cytokines and contribute to the necroinflammatory liver disease.

AB - Background: Hepatitis C infection induces an acute and chronic liver inflammation that may lead to cirrhosis, liver failure, or hepatocarcinoma. Since the role of αβ T lymphocytes in hepatitis C virus (HCV) immunopathology has been analyzed extensively, we investigated the distribution and functional activation of γδ T cell subsets in chronically HCV-infected patients. Materials and Methods: Blood samples and liver biopsies from 35 patients with compensated chronic HCV infection were compared in terms of T cell subset distribution, expression of activation markers, γδ T cell receptor (TCR) repertoire, and pattern of cytokine production. Moreover, we analyzed whether these immunological parameters were associated with other clinical observations (plasma viremia, ALT levels, Ishak index). Results: Differing from peripheral blood distribution, a specific compartmentalization of Vδ1 T cells (p <0.001) was observed in the liver of HCV patients. These cells rep- resented a relevant fraction of intrahepatic T lymphocytes (1.8-8.7%) and expressed the memory/effector phenotype (CD62-L CD45-RO +CD95 +). This phenotype was consistent with selective homing upon antigen recognition. Mitogenic stimulation of Vδ1 + T lymphocytes recruited in the liver revealed the T helper cell type 1 (Th1) pattern of cytokine secretion. Interestingly, the frequency of interferon-γ (IFN-γ)-producing Vδ1 T cells was associated with an higher degree of liver necroinflammation, measured by the Ishak index. Finally, the T-cell repertoire analysis revealed the absence of Vγ selection in the TCR repertoire of intrahepatic Vγ1 T cells. Conclusions: γδ T cell distribution in the peripheral blood differs from the Vδ1 T cell subset because it is policlonally activated and recruited in the liver of chronic HCV-infected patients. During HCV-infection, this T cell subset may release Th1 cytokines and contribute to the necroinflammatory liver disease.

UR - http://www.scopus.com/inward/record.url?scp=0035237929&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035237929&partnerID=8YFLogxK

M3 - Article

C2 - 11474123

AN - SCOPUS:0035237929

VL - 7

SP - 11

EP - 19

JO - Molecular Medicine

JF - Molecular Medicine

SN - 1076-1551

IS - 1

ER -