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

Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
The Journal of Immunology (Impact Factor: 4.92). 07/2009; 183(2):1120-32. DOI: 10.4049/jimmunol.0900182
Source: PubMed


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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Available from: George N Pavlakis
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    • "Another possible explanation is a higher CD8 naive T cells apoptotic death. Unfortunately, as a limitation of the study, we do not dispose of apoptotic rates or PD-1 expression (Petrovas et al. 2009) from CD4 and/or CD8 T cells to clarify this hypothesis and further research is necessary to really clarify this point. Some authors point out that using CD45RA "
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    • "High levels of PD-1 expression on virus-specific CD8+ T cells during chronic human (human immunodeficiency virus [HIV], hepatitis B virus [HBV]), monkey (simian immunodeficiency virus [SIV]), and murine (lymphocytic choriomeningitis virus [LCMV]) infections have been associated with T cell dysfunction and failure to control viral replication [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]. However, Kasprowicz and colleagues have recently reported high levels of PD-1 expression on peripheral blood hepatitis C virus (HCV)-specific CD8+ T cells of infected individuals who clear infection, raising the question of whether PD-1 expression alone is sufficient to confer T cell dysfunction [10]. "
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