Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection

Heiner Wedemeyer, Xiaosong He, Michelina Nascimbeni, Anthony R. Davis, Harry B. Greenberg, Jay H. Hoofnagle, T. Jake Liang, Harvey Alter, Barbara Rehermann

Research output: Contribution to journalArticle

544 Citations (Scopus)

Abstract

The cellular immune response contributes to clearance of hepatitis C virus (HCV) and persists for decades after recovery from infection. The immunological basis for the inefficiency of the cellular immune response in chronically infected persons is not known. Here, we used four HLA-A2 tetramers, specific for two HCV core and two HCV NS3 epitopes, to investigate at the single-cell level effector function and phenotype of HCV-specific CD8+ T cells in 20 chronically infected and 12 long-term recovered patients. Overall, HCV-specific, tetramer+ T cells were more frequently found in PBMCs of chronically infected patients than in those of recovered patients. However, when compared with HCV-tetramer+ T cells of recovered patients, they displayed an impaired proliferative capacity. As a result of the impaired proliferative capacity, HCV-specific T cell lines derived from chronically infected patients displayed less peptide-specific cytotoxicity than those from recovered patients. In addition, proliferation and ex vivo IFN-γ production of HCV-tetramer+ cells, but not influenza-virus-specific T cells, were defective in chronically infected patients and could not be restored by in vitro stimulation with peptide and IL-2. At least three distinct phenotypes of HCV-specific CD8+ T cells were identified and associated with certain functional characteristics. In addition, impairment of proliferative, cytokine, and cytotoxic effector functions of tetramer+ T cells in viremic patients was associated with weak ex vivo HCV-specific CD4+ T cell responses. Thus, the defective functions of HCV-specific CD8+ T cells might contribute to viral persistence in chronically infected patients, and knowledge on their reversibility may facilitate the development of immunotherapeutic vaccines.

Original languageEnglish (US)
Pages (from-to)3447-3458
Number of pages12
JournalJournal of Immunology
Volume169
Issue number6
StatePublished - Sep 15 2002
Externally publishedYes

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Chronic Hepatitis C
Virus Diseases
Hepacivirus
T-Lymphocytes
Cellular Immunity
Phenotype
HLA-A2 Antigen
Peptides
Orthomyxoviridae
Interleukin-2
Epitopes
Vaccines
Cytokines
Cell Line

ASJC Scopus subject areas

  • Immunology

Cite this

Wedemeyer, H., He, X., Nascimbeni, M., Davis, A. R., Greenberg, H. B., Hoofnagle, J. H., ... Rehermann, B. (2002). Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. Journal of Immunology, 169(6), 3447-3458.

Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. / Wedemeyer, Heiner; He, Xiaosong; Nascimbeni, Michelina; Davis, Anthony R.; Greenberg, Harry B.; Hoofnagle, Jay H.; Liang, T. Jake; Alter, Harvey; Rehermann, Barbara.

In: Journal of Immunology, Vol. 169, No. 6, 15.09.2002, p. 3447-3458.

Research output: Contribution to journalArticle

Wedemeyer, H, He, X, Nascimbeni, M, Davis, AR, Greenberg, HB, Hoofnagle, JH, Liang, TJ, Alter, H & Rehermann, B 2002, 'Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection', Journal of Immunology, vol. 169, no. 6, pp. 3447-3458.
Wedemeyer H, He X, Nascimbeni M, Davis AR, Greenberg HB, Hoofnagle JH et al. Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. Journal of Immunology. 2002 Sep 15;169(6):3447-3458.
Wedemeyer, Heiner ; He, Xiaosong ; Nascimbeni, Michelina ; Davis, Anthony R. ; Greenberg, Harry B. ; Hoofnagle, Jay H. ; Liang, T. Jake ; Alter, Harvey ; Rehermann, Barbara. / Impaired effector function of hepatitis C virus-specific CD8+ T cells in chronic hepatitis C virus infection. In: Journal of Immunology. 2002 ; Vol. 169, No. 6. pp. 3447-3458.
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