HIV-1-specific cytotoxicity is preferentially mediated by a subset of CD8+ T cells producing both interferon-γ and tumor necrosis factor-α

被引:104
作者
Lichterfeld, M
Yu, XG
Waring, MT
Mui, SK
Johnston, MN
Cohen, D
Addo, MM
Zaunders, J
Alter, G
Pae, E
Strick, D
Allen, TM
Rosenberg, ES
Walker, BD
Altfeld, M
机构
[1] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA
[2] Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA
[3] Fenway Community Hlth Care Ctr, Boston, MA USA
[4] St Vincents Hosp, Ctr Immunol, Sydney, NSW 2010, Australia
[5] Howard Hughes Med Inst, Chevy Chase, MD USA
关键词
D O I
10.1182/blood-2003-12-4341
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 consider- able intraindividual and interindividual differences among epitope-specific T-cell effector functions: while the frequency of HIV-1-specific CD8(+) T cells secreting interferon-gamma but no tumor necrosis factor-alpha (TNF-alpha) following antigenic stimulation was only weakly correlated to their cytotoxic activity (R = 0.05, P = .57), a subset of CD8(+) T cells secreting both interferon-gamma and TNF-a 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-gamma 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-gamma and TNF-alpha. (C) 2004 by The American Society of Hematology.
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页码:487 / 494
页数:8
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