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Differential association of programmed death-1 and CD57 with ex vivo survival of CD8+ T cells in HIV infection
Journal article   Open access   Peer reviewed

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, …
The Journal of immunology (1950), v 183(2), pp 1120-1132
15 Jul 2009
PMID: 19564339
url
https://www.jimmunol.org/content/jimmunol/183/2/1120.full.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.4049/jimmunol.0900182View
Published, Version of Record (VoR) Open

Abstract

Antigens, CD - metabolism Antigens, CD - physiology Apoptosis Apoptosis Regulatory Proteins - metabolism Apoptosis Regulatory Proteins - physiology CD57 Antigens - physiology CD8-Positive T-Lymphocytes - pathology Cell Survival Cells, Cultured Cytomegalovirus - immunology fas Receptor HIV Infections - immunology HIV Infections - pathology HIV-1 - immunology Humans Programmed Cell Death 1 Receptor Protein Transport
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.

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Web of Science research areas
Immunology
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