title: Differential association of programmed death-1 and CD57 with ex vivo survival of CD8+ T cells in HIV infection.
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-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.
authors: Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA. petrovasc@mail.nih.gov
authors: Constantinos
authors: C
authors: Petrovas
authors: Benjamin
authors: B
authors: Chaon
authors: David R
authors: DR
authors: Ambrozak
authors: David A
authors: DA
authors: Price
authors: J Joseph
authors: JJ
authors: Melenhorst
authors: Brenna J
authors: BJ
authors: Hill
authors: Christof
authors: C
authors: Geldmacher
authors: Joseph P
authors: JP
authors: Casazza
authors: Pratip K
authors: PK
authors: Chattopadhyay
authors: Mario
authors: M
authors: Roederer
authors: Daniel C
authors: DC
authors: Douek
authors: Yvonne M
authors: YM
authors: Mueller
authors: Jeffrey M
authors: JM
authors: Jacobson
authors: Viraj
authors: V
authors: Kulkarni
authors: Barbara K
authors: BK
authors: Felber
authors: George N
authors: GN
authors: Pavlakis
authors: Peter D
authors: PD
authors: Katsikis
authors: Richard A
authors: RA
authors: Koup
mesh_terms: D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism / Q000502:physiology*; D018959:CD57 Antigens / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D002470:Cell Survival; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D061026:Programmed Cell Death 1 Receptor; D021381:Protein Transport; D019014:fas Receptor
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018959:CD57 Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D019014:fas Receptor