BACKGROUND: Hepatitis C infection induces an acute and chronic liver inflammation that may lead to cirrhosis, liver failure, or hepatocarcinoma. Since the role of alphabeta T lymphocytes in hepatitis C virus (HCV) immunopathology has been analyzed extensively, we investigated the distribution and functional activation of gammadelta 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, gammadelta 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 Vdelta1 T cells (p < 0.001) was observed in the liver of HCV patients. These cells represented 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 Vdelta1 + T lymphocytes recruited in the liver revealed the T helper cell type 1 (Th1) pattern of cytokine secretion. Interestingly, the frequency of interferon-gamma (IFN-gamma)-producing Vdelta1 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 Vgamma selection in the TCR repertoire of intrahepatic Vdelta1 T cells. CONCLUSIONS: gammadelta T cell distribution in the peripheral blood differs from the Vdelta1 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.
BACKGROUND:Hepatitis C infection induces an acute and chronic liver inflammation that may lead to cirrhosis, liver failure, or hepatocarcinoma. Since the role of alphabeta T lymphocytes in hepatitis C virus (HCV) immunopathology has been analyzed extensively, we investigated the distribution and functional activation of gammadelta T cell subsets in chronically HCV-infectedpatients. 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, gammadelta 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 Vdelta1 T cells (p < 0.001) was observed in the liver of HCVpatients. These cells represented 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 Vdelta1 + T lymphocytes recruited in the liver revealed the T helper cell type 1 (Th1) pattern of cytokine secretion. Interestingly, the frequency of interferon-gamma (IFN-gamma)-producing Vdelta1 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 Vgamma selection in the TCR repertoire of intrahepatic Vdelta1 T cells. CONCLUSIONS: gammadelta T cell distribution in the peripheral blood differs from the Vdelta1 T cell subset because it is policlonally activated and recruited in the liver of chronic HCV-infectedpatients. During HCV-infection, this T cell subset may release Th1 cytokines and contribute to the necroinflammatory liver disease.
Authors: Bradley S Schneider; Lynn Soong; Lark L Coffey; Heather L Stevenson; Charles E McGee; Stephen Higgs Journal: PLoS One Date: 2010-07-22 Impact factor: 3.240
Authors: Adam G Laing; Anna Lorenc; Irene Del Molino Del Barrio; Abhishek Das; Matthew Fish; Leticia Monin; Miguel Muñoz-Ruiz; Duncan R McKenzie; Thomas S Hayday; Isaac Francos-Quijorna; Shraddha Kamdar; Magdalene Joseph; Daniel Davies; Richard Davis; Aislinn Jennings; Iva Zlatareva; Pierre Vantourout; Yin Wu; Vasiliki Sofra; Florencia Cano; Maria Greco; Efstathios Theodoridis; Joshua D Freedman; Sarah Gee; Julie Nuo En Chan; Sarah Ryan; Eva Bugallo-Blanco; Pärt Peterson; Kai Kisand; Liis Haljasmägi; Loubna Chadli; Philippe Moingeon; Lauren Martinez; Blair Merrick; Karen Bisnauthsing; Kate Brooks; Mohammad A A Ibrahim; Jeremy Mason; Federico Lopez Gomez; Kola Babalola; Sultan Abdul-Jawad; John Cason; Christine Mant; Jeffrey Seow; Carl Graham; Katie J Doores; Francesca Di Rosa; Jonathan Edgeworth; Manu Shankar-Hari; Adrian C Hayday Journal: Nat Med Date: 2020-08-17 Impact factor: 87.241