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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-03-0791. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-03-0791v1 101/1/226    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Zhang, D. Articles by Lieberman, J. Search for Related Content PubMed PubMed Citation Articles by Zhang, D. Articles by Lieberman, J. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2003, Vol. 101, No. 1, pp. 226-235 IMMUNOBIOLOGY Most antiviral CD8 T cells during chronic viral infection do not express high levels of perforin and are not directly cytotoxic Dong Zhang, Premlata Shankar, Zhan Xu, Brooke Harnisch, Gang Chen, Christoph Lange, Sandra J. Lee, Hernan Valdez, Michael M. Lederman, and Judy Lieberman From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH. Despite the frequency of HIV-specific CD8 T cells, most HIV-infected patients do not control viral replication without antiviral drugs. Although CD8 T cells are important in containing acute HIV and simian immunodeficiency virus (SIV) infection, CD8 T-cell functions are compromised in chronic infection. To investigate whether functional deficits are specific to HIV, the phenotypic and functional properties of HIV, Epstein-Barr virus (EBV), and cytomegalovirus (CMV)-specific CD8 T cells, labeled with HLA A2.1 or B8 tetramers, were compared in 35 HIV-infected and 9 healthy donors. Cytotoxic T lymphocytes express the cytolytic molecules perforin and granzymes, and are thought to be CD45RA+CD27. Although most HIV- specific cells are antigen experienced and express granzyme A (median, 85%), few express high levels of perforin (median, 10%) or CD45RA (median, 14%) or have down-modulated CD27 (median, 12%). Perforin expression by HIV-specific cells is not significantly different from that of EBV- or CMV-specific cells in the same donors or in healthy donors. EBV- and CMV-specific cells, like HIV-specific cells, are often not cytotoxic when tested directly ex vivo. HIV-specific T-cell expression of other phenotypic markers is similar to that of EBV- and CMV-specific CD8 T cells in healthy donors. However, CMV-specific cells (and, to a lesser extent, EBV-specific cells) in HIV-infected donors are more likely to be CD27, CD45RA+, and GzmA+. These results suggest that the chance to eradicate an infection by T-cell-mediated lysis may be undermined once an infection becomes chronic. Impaired antiviral cytotoxicity during chronic infection is not specific to HIV but likely represents the immune response to chronic antigenic exposure. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Iannello, O. Debbeche, S. Samarani, and A. 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