TY - JOUR
T1 - Differential association of programmed death-1 and CD57 with ex vivo survival of CD8+ T cells in HIV infection
AU - Petrovas, Constantinos
AU - Chaon, Benjamin
AU - Ambrozak, David R.
AU - Price, David A.
AU - Melenhorst, J. Joseph
AU - Hill, Brenna J.
AU - Geldmacher, Christof
AU - Casazza, Joseph P.
AU - Chattopadhyay, Pratip K.
AU - Roederer, Mario
AU - Douek, Daniel C.
AU - Mueller, Yvonne M.
AU - Jacobson, Jeffrey M.
AU - Kulkarni, Viraj
AU - Felber, Barbara K.
AU - Pavlakis, George N.
AU - Katsikis, Peter D.
AU - Koup, Richard A.
PY - 2009/7/15
Y1 - 2009/7/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.0900182
DO - 10.4049/jimmunol.0900182
M3 - Article
C2 - 19564339
AN - SCOPUS:70249122418
SN - 0022-1767
VL - 183
SP - 1120
EP - 1132
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -