Increased frequency of IFN-gamma-producing peripheral CD8+ T cells with memory-phenotype in patients with chronic hepatitis C.
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.
Murata
Masayuki
M
Environmental Medicine and Infectious Diseases, Internal Medicine, Faculty of Medical Sciences Kyushu University, Fukuoka, Japan.
Nabeshima
Shigeki
S
Maeda
Naoyasu
N
Nakashima
Hisashi
H
Kashiwagi
Seizaburo
S
Hayashi
Jun
J
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets
D007371:Interferon-gamma