Differential association of programmed death-1 and CD57 with ex vivo survival of CD8+ T cells in HIV infection.
Differential association of programmed death-1 and CD57 with ex vivo survival of CD8+ T cells in HIV infection.
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DOI：
10.4049/jimmunol.0900182
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发表时间：
2009-07-15
期刊：
影响因子：
--
通讯作者：
Koup RA
中科院分区：
文献类型：
--
作者：
Petrovas C;Chaon B;Ambrozak DR;Price DA;Melenhorst JJ;Hill BJ;Geldmacher C;Casazza JP;Chattopadhyay PK;Roederer M;Douek DC;Mueller YM;Jacobson JM;Kulkarni V;Felber BK;Pavlakis GN;Katsikis PD;Koup RA
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-Rα, 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-1LCD57H phenotype exhibiting lower levels of cell death. The majority of HIV-specific CD8+ T cells were found to express a PD-1HCD57L or PD-1HCD57H 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.
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