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Blood, 15 July 2004, Vol. 104, No. 2, pp. 478-486. Prepublished online as a Blood First Edition Paper on March 25, 2004; DOI 10.1182/blood-2003-12-4395. This Article Full Text (PDF) All Versions of this Article: 2003-12-4395v1 104/2/478    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nascimbeni, M. Articles by Rehermann, B. Search for Related Content PubMed PubMed Citation Articles by Nascimbeni, M. Articles by Rehermann, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 2, 2004 Accepted March 11, 2004 Peripheral CD4/CD8 Double-Positive T cells are Differentiated Effector Memory Cells With Antiviral Functions Michelina Nascimbeni, Eui-Cheol Shin, Luis Chiriboga, David E Kleiner, and Barbara Rehermann* Liver Diseases Section, Digestive Diseases Branch, NIDDK, National Institutes of Health, DHHS, Bethesda, MD, USA Department of Pathology, Bellevue Hospital, NYU School of Medicine, New York, NY, USA Laboratory of Pathology, NCI, National Institutes of Health, DHHS, Bethesda, MD, USA * Corresponding author; email: Rehermann{at}nih.gov. Although an increased frequency of CD4/CD8 double-positive T cells has been observed in the peripheral blood during viral infections, their role, function and biological significance are still poorly understood. Here we demonstrate that the circulating CD4/CD8 double-positive 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 double-positive than single-positive cells displayed a Th1/Tc1 cytokine profile and proliferated. Ex vivo, more double-positive than single-positive cells exhibited a differentiated phenotype. Accordingly, their lower 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 double-positive cells were demonstrated in situ at the site of persistent viral infection, i.e. in the liver during chronic hepatitis C. Finally, a prospective analysis of HCV infection in a chimpanzee, the only animal model for HCV infection, showed a close correlation between the frequency of activated CD4/CD8 double-positive cells and viral kinetics. Collectively, these findings demonstrate that peripheral CD4/CD8 double-positive 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Zloza, J. M. Schenkel, A. R. Tenorio, J. A. Martinson, P. M. Jeziorczak, and L. Al-Harthi Potent HIV-specific responses are enriched in a unique subset of CD8+ T cells that coexpresses CD4 on its surface Blood, October 29, 2009; 114(18): 3841 - 3853. [Abstract] [Full Text] [PDF] Z. Dai, C. J. Turtle, G. C. Booth, S. R. Riddell, T. A. Gooley, A. M. Stevens, T. Spies, and V. 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