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

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-1^LCD57^H phenotype exhibiting lower levels of cell death. The majority of HIV-specific CD8⁺ T cells were found to express a PD-1^HCD57^L or PD-1^HCD57 ^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.