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Blood, 15 July 2004, Vol. 104, No. 2, pp. 487-494. Prepublished online as a Blood First Edition Paper on April 1, 2004; DOI 10.1182/blood-2003-12-4341. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4341v1 104/2/487    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 Lichterfeld, M. Articles by Altfeld, M. Search for Related Content PubMed PubMed Citation Articles by Lichterfeld, M. Articles by Altfeld, M. Related Collections Immunobiology Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY HIV-1–specific cytotoxicity is preferentially mediated by a subset of CD8+ T cells producing both interferon- and tumor necrosis factor– Mathias Lichterfeld, Xu G. Yu, Michael T. Waring, Stanley K. Mui, Mary N. Johnston, Daniel Cohen, Marylyn M. Addo, John Zaunders, Galit Alter, Eunice Pae, Daryld Strick, Todd M. Allen, Eric S. Rosenberg, Bruce D. Walker, and Marcus Altfeld From the Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, and the Fenway Community Health Care Center, Boston, MA; the Centre for Immunology, St Vincent's Hospital, Sydney, Australia; and the Howard Hughes Medical Institute, Chevy Chase, MD. CD8+ T cells play a crucial role in the control of viral infections by direct elimination of infected cells and secretion of a number of soluble factors. Recent data suggest that HIV-1-specific CD8+ T cell subsets may differ in their ability to exert these effector functions. Here, we directly compared the cytokine secretion patterns and cytotoxic capacity of HIV-1-specific CD8+ T cells, using a flow-cytometric cytotoxicity assay based on caspase-3 activation in dying target cells. These experiments revealed considerable intraindividual and interindividual differences among epitope-specific T-cell effector functions: while the frequency of HIV-1-specific CD8+ T cells secreting interferon- but no tumor necrosis factor- (TNF-) following antigenic stimulation was only weakly correlated to their cytotoxic activity (R = 0.05, P = .57), a subset of CD8+ T cells secreting both inter-feron- and TNF- was substantially more strongly associated with cytotoxicity (R = 0.67, P < .001). This subset of CD8+ T cells also exhibited stronger intracellular perforin expression and more pronounced direct ex vivo HIV-1-specific cytoxicity than CD8+ T cells secreting solely interferon- following sorting of these subpopulations according to their cytokine profile. These results suggest that HIV-1-specific cytotoxicity of CD8+ T cells is preferentially mediated by a subset of CD8+ T cells secreting both interferon- and TNF-. (Blood. 2004;104:487-494) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. R. Bailey, K. O'Connell, H.-C. Yang, Y. Han, J. Xu, B. Jilek, T. M. Williams, S. C. Ray, R. F. Siliciano, and J. N. Blankson Transmission of Human Immunodeficiency Virus Type 1 from a Patient Who Developed AIDS to an Elite Suppressor J. Virol., August 1, 2008; 82(15): 7395 - 7410. [Abstract] [Full Text] [PDF] D. G. Brooks, A. M. Lee, H. Elsaesser, D. B. McGavern, and M. 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