共 35 条
HIV-1-specific cytotoxicity is preferentially mediated by a subset of CD8+ T cells producing both interferon-γ and tumor necrosis factor-α
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作者:

Lichterfeld, M
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Yu, XG
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Waring, MT
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Mui, SK
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Johnston, MN
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Cohen, D
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Addo, MM
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Zaunders, J
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Alter, G
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Pae, E
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA

Strick, D
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA

Allen, TM
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA

Rosenberg, ES
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA

Walker, BD
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA

Altfeld, M
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机构: Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA
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
来源:
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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Knabenhans, C
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Ellefsen, K
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Nobile, M
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Appay, V
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Rizzardi, GP
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Fleury, S
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Lipp, M
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Förster, R
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Rowland-Jones, S
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Sékaly, RP
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McMichael, AJ
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Pantaleo, G
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Univ Lausanne, CHU Vaudois, Dept Med, Div Immunol & Allergy,Lab AIDS Immunopathogenesis, CH-1011 Lausanne, Switzerland Univ Lausanne, CHU Vaudois, Dept Med, Div Immunol & Allergy,Lab AIDS Immunopathogenesis, CH-1011 Lausanne, Switzerland
[10]
CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection
[J].
Chen, G
;
Shankar, P
;
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;
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;
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;
Wu, LJ
;
Manjunath, N
;
Lieberman, J
.
BLOOD,
2001, 98 (01)
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Chen, G
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机构: Ctr Blood Res, Boston, MA 02115 USA

Shankar, P
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Lange, C
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Valdez, H
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Skolnik, PR
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Wu, LJ
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Manjunath, N
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Lieberman, J
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