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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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-1HCD57 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.

Original languageEnglish (US)
Pages (from-to)1120-1132
Number of pages13
JournalJournal of Immunology
Volume183
Issue number2
DOIs
StatePublished - Jul 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Differential association of programmed death-1 and CD57 with ex vivo survival of CD8<sup>+</sup> T cells in HIV infection'. Together they form a unique fingerprint.

Cite this