Peripheral CD4(+)CD8(+) T cells are differentiated effector memory cells with antiviral functions

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Although an increased frequency of CD4(+)CD8(+) T cells has been observed in the peripheral blood during viral infections, their role, function, and biologic significance are still poorly understood. Here we demonstrate that the circulating CD4+CD8+ T-cell population contains mature effector memory lymphocytes specific for antigens of multiple past, latent, and high-level persistent viral infections. Upon in vitro antigenic challenge, a higher frequency of CD4+CD8+ than single-positive cells displayed a T helper 1/T cytotoxic 1 (Th1/Tc1) cytokine profile and proliferated. Ex vivo, more double-positive than single-positive cells exhibited a differentiated phenotype. Accordingly, their lower T-cell receptor excision circles (TREC) content and shorter telomeres proved they had divided more frequently than single-positive cells. Consistent with expression of the tissue-homing marker CXCR3, CD4(+)CD8(+) T cells were demonstrated in situ at the site of persistent viral infection (le, in the liver during chronic hepatitis C). Finally, a prospective analysis of hepatitis C virus (HCV) infection in a chimpanzee, the only animal model for HCV infection, showed a close correlation between the frequency of activated CD4(+)CD8(+) T cells and viral kinetics. Collectively, these findings demonstrate that peripheral CD4(+)CD8(+) T cells take part in the adaptive immune response against infectious pathogens and broaden the perception of the T-cell populations involved in antiviral immune responses. (C) 2004 by The American Society of Hematology.
Publisher
AMER SOC HEMATOLOGY
Issue Date
2004-07
Language
English
Article Type
Article
Keywords

HEPATITIS-C VIRUS; CELLULAR IMMUNE-RESPONSES; PERSISTENT EXPANSIONS; CYTOTOXIC ACTIVITY; EXPRESS CD4; HUMAN LIVER; IN-VIVO; LYMPHOCYTES; BLOOD; INFECTION

Citation

BLOOD, v.104, no.2, pp.478 - 486

ISSN
0006-4971
DOI
10.1182/blood-2003-12-4395
URI
http://hdl.handle.net/10203/85719
Appears in Collection
MSE-Journal Papers(저널논문)
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