Loss of DNAM-1 contributes to CD8+ T-cell exhaustion in chronic HIV-1 infection

被引：46

作者：

Cella, Marina ^{[1
]}

Presti, Rachel ^{[1
]}

Vermi, William ^{[2
]}

Lavender, Kerry ^{[3
]}

Turnbull, Emma ^{[3
]}

Ochsenbauer-Jambor, Christina ^{[4
]}

Kappes, John C. ^{[4
]}

Ferrari, Guido ^{[5
]}

Kessels, Lisa ^{[6
]}

Williams, Ian ^{[7
]}

McMichael, Andrew J. ^{[8
]}

Haynes, Barton F. ^{[5
]}

Borrow, Persephone ^{[3
]}

Colonna, Marco ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA

[2] Univ Brescia, Spedali Civili, Dept Pathol 1, Brescia, Italy

[3] Univ Oxford, Jenner Inst, Compton, England

[4] Univ Alabama Birmingham, Birmingham, AL USA

[5] Duke Univ, Med Ctr, Durham, NC USA

[6] Washington Univ, Sch Med, AIDS Clin Trial Unit, St Louis, MO 63110 USA

[7] Mortimer Market Ctr, Ctr Sexual Hlth & HIV Res, London, England

[8] Univ Oxford, Human Immunol Unit, Weatherall Inst Mol Med, MRC, Oxford, England

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2010年 / 40卷 / 04期

关键词：

Co-stimulation; Exhaustion; HIV-1; LYMPHOCYTES; PD-1;

D O I：

10.1002/eji.200940234

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The hallmark of chronic viral infections is a progressive exhaustion of antigen-specific CD8(+) T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8(+) T cells that makes them dysfunctional. Here, we show that during human chronic HIV-1 infection, a CD8(+) T-cell positive costimulatory pathway mediated by DNAX-activating molecule-1 is also disrupted. Thus, DNAX-activating molecule-1 downregulation on CD8(+) T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection.

引用

页码：949 / 954

页数：6

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