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

作者：Petrovas Constantinos^*; Chaon Benjamin; Ambrozak David R; Price David A; Melenhorst J Joseph; Hill Brenna J; Geldmacher Christof; Casazza Joseph P; Chattopadhyay Pratip K; Roederer Mario; Douek Daniel C; Mueller Yvonne M; Jacobson Jeffrey M; Kulkarni Viraj; Felber Barbara K; Pavlakis George N; Katsikis Peter D; Koup Richard A

来源：The Journal of Immunology, 2009, 183(2): 1120-1132.

DOI：10.4049/jimmunol.0900182

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.

• 出版日期2009-7-15