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Differential association of programmed death-1 and CD57 with ex vivo survival of CD8+ T cells in HIV infection

Petrovas, Constantinos, Chaon, Benjamin, Ambrozak, David R., Price, David, 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. and Koup, Richard A. 2009. Differential association of programmed death-1 and CD57 with ex vivo survival of CD8+ T cells in HIV infection. The Journal of Immunology 183 (2) , pp. 1120-1132. 10.4049/jimmunol.0900182

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 04 Jun 2017 03:57

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