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 language | English |
|---|---|
| Pages (from-to) | 11-19 |
| Number of pages | 9 |
| Journal | Molecular medicine (Cambridge, Mass.) |
| Volume | 7 |
| Issue number | 1 |
| Publication status | Published - 2001 |
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- Genetics
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Vδ1T Lymphocytes Expressing a Th1 Phenotype Are the Major γδ T Cell Subset Infiltrating the Liver of HCV-infected Persons. / Agrati, Chiara; D'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 journal › Article
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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'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.
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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 -