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

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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 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 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 Vδ1 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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Acknowledgments

This work was supported by grants from the Current and Finalized Research Projects of the Italian Ministry of Health. C.A. is a fellow of the Institute for Infectious Diseases, L. Spallanzani. We thank M. Lupi, G. Cianca, C. Vasile, L. Bolognesi and D. Menna for clinical monitoring, organization, support and dedication to patient care. Finally we thank E. Akinde for careful reading of the manuscript.

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Authors and Affiliations

  1. International Centre for AIDS and Emerging Infections, National Institute for Infectious Diseases (IRCCS) Lazzaro Spallanzani, Rome, Italy

    Chiara Agrati, Giampiero D’Offizi, Vittorio Colizzi &  Fabrizio Poccia

  2. 4th Clinical Division, National Institute for Infectious Diseases (IRCCS) Lazzaro Spallanzani, Rome, Italy

    Giampiero D’Offizi & Pasquale Narciso

  3. Centro di Riferimento AIDS e Servizio di Epidemiologia Delle Malattie Infettive, National Institute for Infectious Diseases (IRCCS) Lazzaro Spallanzani, Rome, Italy

    Giuseppe Ippolito

  4. Laboratory of Clinical Pathology of the National Institute for Infectious Diseases (IRCCS) Lazzaro Spallanzani, Via Portuense 292, 00149, Rome, Italy

    Fabrizio Poccia

  5. Chiron S.p.a, Siena, Italy

    Sergio Abrignani

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  1. Chiara Agrati
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  2. Giampiero D’Offizi
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  5. Giuseppe Ippolito
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  7. Fabrizio Poccia
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Correspondence to Fabrizio Poccia.

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Agrati, C., D’Offizi, G., Narciso, P. et al. Vδ1T Lymphocytes Expressing a Th1 Phenotype Are the Major γδ T Cell Subset Infiltrating the Liver of HCV-infected Persons. Mol Med 7, 11–19 (2001). https://doi.org/10.1007/BF03401834

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