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Expansion of Human Peripheral Blood γδ T Cells using Zoledronate
Published on: September 9, 2011
Increased frequency of IFN-gamma-producing peripheral CD8+ T cells with memory-phenotype in patients with chronic
Masayuki Murata1, Shigeki Nabeshima, Naoyasu Maeda
1Environmental Medicine and Infectious Diseases, Internal Medicine, Faculty of Medical Sciences Kyushu University, Fukuoka, Japan.
Insights
Peripheral CD8(+) T cells producing interferon-gamma (IFN-gamma) and memory CD8(+) T cells are more common in chronic hepatitis C patients. These activated T cells may contribute to liver damage.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Chronic hepatitis C (HCV) is a significant global health concern.
- Understanding the role of T cells in HCV pathogenesis is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the cytokine production capacity and phenotypic characteristics of peripheral CD8(+) T cells in patients with chronic hepatitis C.
- To determine the association between CD8(+) T cell profiles and liver damage in chronic HCV infection.
Main Methods:
- Three-color flow cytometry was used to analyze peripheral blood mononuclear cells from 31 chronic HCV patients and 22 healthy controls.
- Cells were stained for CD8, intracellular interferon-gamma (IFN-gamma), interleukin-4 (IL-4), CD28, and CD45RA.
- Stimulation with PMA plus ionomycin was performed to assess cytokine production capacity.
Main Results:
- IFN-gamma-producing CD8(+) T cells were significantly more frequent in HCV patients than in controls.
- Memory CD8(+) T cells (CD45RA(-)CD28(+)CD8(+)) were also more prevalent in patients.
- No significant correlation was found between IFN-gamma-producing CD8(+) T cells and HCV RNA levels or ALT levels.
Conclusions:
- Functionally T cytotoxic type 1 and memory CD8(+) T cells are predominant in the peripheral blood of chronic hepatitis C patients.
- These activated CD8(+) T cells are associated with liver damage in chronic HCV infection.
- The findings suggest a potential role for these T cells in HCV-mediated liver injury.
Abstract:
To identify the capacity for cytokine production and the phenotypic characteristics of peripheral CD8(+) T cells in patients with chronic hepatitis C, 31 patients with chronic hepatitis C and 22 healthy controls were studied at the single cell level by three-color flow cytometry. Whole blood was stained with surface CD8, intracellular interferon-gamma (IFN-gamma), and interleukin-4 (IL-4), surface CD8, CD28, and intracellular IFN-gamma after stimulation with PMA plus ionomycin, and then surface CD8, CD45RA, and CD28. IFN-gamma-producing peripheral CD8(+) T cells were found frequently in patients than in controls (P < 0.05), whereas IL-4-producing peripheral CD8(+) T cells were not. Although the frequency of peripheral CD28(+)CD8(+) and CD28(-)CD8(+) T cells in patients was not different from that of controls, CD28(+)CD8(+) T cells exceeded CD28(-)CD8(+) T cells in the capacity for IFN-gamma-production after mitogenic stimulation (P < 0.01). In a more detailed analysis of the CD28(+)CD8(+) T cells, CD45RA(-)CD28(+)CD8(+) T cells, defined phenotypically as memory cells, were found frequently in patients than in controls (P < 0.05). There were no significant correlations between the frequency of IFN-gamma-producing peripheral CD8(+) T cells and hepatitis C virus RNA level or serum alanine aminotransferase level in patients. These data suggest that functionally T cytotoxic type 1 and memory CD8(+) T cells are predominant in the peripheral blood of chronic hepatitis C patients and that such activated CD8(+) T cells are associated with liver damage.
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