Differential Association of Programmed Death-1 and CD57 with Ex Vivo Survival of CD8+ T Cells in HIV Infection

被引：87

作者：

Petrovas, Constantinos ^{[1
]}

Chaon, Benjamin ^{[1
]}

Ambrozak, David R. ^{[1
]}

Price, David A. ^{[2
,4
]}

Melenhorst, J. Joseph ^{[5
]}

Hill, Brenna J. ^{[2
]}

Geldmacher, Christof ^{[1
]}

Casazza, Joseph P. ^{[1
]}

Chattopadhyay, Pratip K. ^{[3
]}

Roederer, Mario ^{[3
]}

Douek, Daniel C. ^{[2
]}

Mueller, Yvonne M. ^{[6
,7
]}

Jacobson, Jeffrey M. ^{[6
,7
]}

Kulkarni, Viraj ^{[8
]}

Felber, Barbara K. ^{[8
]}

Pavlakis, George N. ^{[9
]}

Katsikis, Peter D. ^{[6
,7
]}

Koup, Richard A. ^{[1
]}

机构：

[1] NIAID, Immunol Lab, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20814 USA

[2] NIAID, Human Immunol Sect, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20814 USA

[3] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20814 USA

[4] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales

[5] NHLBI, Hematol Branch, Natl Inst Hlth, Bethesda, MD 20814 USA

[6] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19102 USA

[7] Drexel Univ, Coll Med, Dept Med, Philadelphia, PA 19102 USA

[8] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA

[9] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 02期

关键词：

FAS-MEDIATED APOPTOSIS; PD-1; EXPRESSION; CD95/FAS-INDUCED APOPTOSIS; ACTIVATION; RECEPTOR; TRANSLOCATION; LYMPHOCYTES; RESPONSES; REGULATORS; CYTOKINES;

D O I：

10.4049/jimmunol.0900182

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV+ donors. High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. The Journal of Immunology, 2009, 183: 1120-1132.

引用

页码：1120 / 1132

页数：13

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