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Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
Published on: September 25, 2019
Visual demonstration of hepatitis C virus-specific memory CD8(+) T-cell expansion in patients with acute hepatitis C
Y Sobao1, H Tomiyama, S Nakamura
1Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto, Japan.
Insights
Hepatitis C virus (HCV)-specific CD8(+) T cells are more abundant in acute infections. These cells in acute HCV display a memory phenotype, unlike those in chronic HCV, indicating distinct immune responses.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Hepatitis C virus (HCV) infection establishes chronic disease in a majority of individuals.
- Understanding the role of CD8(+) T cells in HCV pathogenesis is crucial for developing effective therapies.
Purpose of the Study:
- To quantitatively analyze HCV-specific CD8(+) T cells in patients with acute and chronic hepatitis C.
- To characterize the phenotype and functional markers of these T cells during different phases of HCV infection.
Main Methods:
- Quantitative analysis of peripheral blood mononuclear cells (PBMCs) using flow cytometry.
- Utilized HLA-B*3501-HCV epitope tetrameric complexes to identify specific CD8(+) T cells.
- Assessed T cell phenotypes (CD28, CD45RA) and intracellular perforin expression.
Main Results:
- HCV-specific CD8(+) T cells were detected at 0.05%-0.12% in chronic hepatitis C.
- Frequencies of these cells were 3-5 times higher in acute HCV compared to recovery or chronic phases.
- Expanding CD8(+) T cells in acute HCV predominantly showed a memory phenotype (CD28(+)CD45RA(-)) and lacked perforin.
Conclusions:
- A higher number of circulating HCV-specific CD8(+) T cells, primarily memory T cells, are present during the acute phase of HCV infection.
- The distinct phenotype of CD8(+) T cells in acute versus chronic HCV suggests different immune response dynamics.
Abstract:
Hepatitis C virus (HCV)-specific CD8(+) T cells in peripheral blood mononuclear cells (PBMCs) from patients infected with HCV were quantitatively analyzed by flow cytometry using an HLA-B*3501-HCV epitope tetrameric complex. In chronic hepatitis C, tetramer(+)CD8(+) T cells were detected at frequencies ranging from 0.05% to 0.12% of total CD8(+) T cells. The number of tetramer(+)CD8(+) T cells in acute phase PBMCs from patients with acute hepatitis C was about 3 to 5 times higher than in recovery phase PBMCs from the same patients and in PBMCs from patients with chronic hepatitis C. Expanding tetramer(+)CD8(+) T cells in PBMCs from patients with acute hepatitis C express a CD28(+)CD45RA(-) memory T-cell phenotype. In contrast, tetramer(+)CD8(+) T cells in PBMCs from patients with chronic hepatitis C did not predominantly express this phenotype. These tetramer(+)CD8(+) T cells did not have perforin in their cytoplasma. The present study visually showed that a high number of circulating HCV-specific CD8(+) T cells in acute phase PBMCs from patients with acute hepatitis C are mostly memory T cells.
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