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

共 16 条

[11] NORMAL T-LYMPHOCYTES CAN EXPRESS 2 DIFFERENT T-CELL RECEPTOR BETA-CHAINS - IMPLICATIONS FOR THE MECHANISM OF ALLELIC EXCLUSION [J].

PADOVAN, E ;

GIACHINO, C ;

CELLA, M ;

VALITUTTI, S ;

ACUTO, O ;

LANZAVECCHIA, A .

JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (04) :1587-1591

[12] PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection [J].

Petrovas, Constantinos ;

Casazza, Joseph P. ;

Brenchley, Jason M. ;

Price, David A. ;

Gostick, Emma ;

Adams, William C. ;

Precopio, Melissa L. ;

Schacker, Timothy ;

Roederer, Mario ;

Douek, Daniel C. ;

Koup, Richard A. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (10) :2281-2292

[13] The sound of silence: modulating anergy in T lymphocytes [J].

Sabil, Samuel D. ;

Deenick, Elissa K. ;

Ohashi, Pamela S. .

CURRENT OPINION IN IMMUNOLOGY, 2007, 19 (06) :658-664

[14] CD8 T cell dysfunction during chronic viral infection [J].

Shin, Haina ;

Wherry, E. John .

CURRENT OPINION IN IMMUNOLOGY, 2007, 19 (04) :408-415

[15] Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction [J].

Trautmann, Lydie ;

Janbazian, Loury ;

Chomont, Nicolas ;

Said, Elias A. ;

Gimmig, Sylvain ;

Bessette, Benoit ;

Boulassel, Mohamed-Rachid ;

Delwart, Eric ;

Sepulveda, Homero ;

Balderas, Robert S. ;

Routy, Jean-Pierre ;

Haddad, Elias K. ;

Sekaly, Rafick-Pierre .

NATURE MEDICINE, 2006, 12 (10) :1198-1202

[16] Molecular signature of CD8+ T cell exhaustion during chronic viral infection [J].

Wherry, E. John ;

Ha, Sang-Jun ;

Kaech, Susan M. ;

Haining, W. Nicholas ;

Sarkar, Surojit ;

Kalia, Vandana ;

Subramaniam, Shruti ;

Blattman, Joseph N. ;

Barber, Daniel L. ;

Ahmed, Rafi .

IMMUNITY, 2007, 27 (04) :670-684

← 1 2 →