Frequencies of HCV-specific effector CD4+ T cells by flow cytometry

Correlation with clinical disease stages

Hugo R. Rosen, Camette Miner, Anna W. Sasaki, David Lewinsohn, Andrew J. Conrad, Antony Bakke, H. G Archie Bouwer, David J. Hinrichs

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) is the leading cause of chronic hepatitis, affecting approximately 2% of the world's population. The immune mechanisms responsible for the highly variable natural history in a given individual are unknown. We used a multiparameter flow cytometric technique to functionally and phenotypically characterize HCV-specific effector T cells in the peripheral blood of 32 individuals with different stages of hepatitis C disease (resolved, mild chronic, advanced chronic) and normal controls. We found the highest frequencies of virus-specific effector cells with an activated memory phenotype (CD45RO+CD69+) in subjects who had resolved HCV infection, either spontaneously or with antiviral therapy. Effector cells from patients with resolved infection produced Th1 type cytokines following stimulation with nonstructural antigens (NS3 and NS4), whereas effector cells from chronically infected patients produced Th1 type cytokines predominantly following stimulation with the HCV core antigen. Stimulation with superantigen staphylococcal enterotoxin (SEB) induced the same levels of cytokine production in the different patient groups. Among the HCV-seropositive patients, viral load inversely correlated with the Th1 effector cell response to NS3. Interleukin (IL)-4 was produced only in response to the control antigens, but not in response to the HCV recombinant proteins. Taken together, these findings suggest that a vigorous HCV-specific CD4+ Th1 response, particularly against the nonstructural proteins of the virus, may be associated with viral clearance and protection from disease progression. Prospective studies using this new flow cytometric assay will be required to determine whether antiviral therapy modifies the frequency, specificity, and function of these virus-specific effector cells.

Original languageEnglish (US)
Pages (from-to)190-198
Number of pages9
JournalHepatology
Volume35
Issue number1
DOIs
StatePublished - 2002

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Hepacivirus
Flow Cytometry
T-Lymphocytes
Cytokines
Viruses
Antigens
Antiviral Agents
Superantigens
Th1 Cells
Enterotoxins
Virus Diseases
Chronic Hepatitis
Hepatitis C
Natural History
Viral Load
Recombinant Proteins
Interleukin-4
Disease Progression
Prospective Studies
Phenotype

ASJC Scopus subject areas

  • Hepatology

Cite this

Frequencies of HCV-specific effector CD4+ T cells by flow cytometry : Correlation with clinical disease stages. / Rosen, Hugo R.; Miner, Camette; Sasaki, Anna W.; Lewinsohn, David; Conrad, Andrew J.; Bakke, Antony; Bouwer, H. G Archie; Hinrichs, David J.

In: Hepatology, Vol. 35, No. 1, 2002, p. 190-198.

Research output: Contribution to journalArticle

Rosen, HR, Miner, C, Sasaki, AW, Lewinsohn, D, Conrad, AJ, Bakke, A, Bouwer, HGA & Hinrichs, DJ 2002, 'Frequencies of HCV-specific effector CD4+ T cells by flow cytometry: Correlation with clinical disease stages', Hepatology, vol. 35, no. 1, pp. 190-198. https://doi.org/10.1053/jhep.2002.30293
Rosen, Hugo R. ; Miner, Camette ; Sasaki, Anna W. ; Lewinsohn, David ; Conrad, Andrew J. ; Bakke, Antony ; Bouwer, H. G Archie ; Hinrichs, David J. / Frequencies of HCV-specific effector CD4+ T cells by flow cytometry : Correlation with clinical disease stages. In: Hepatology. 2002 ; Vol. 35, No. 1. pp. 190-198.
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