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-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.
Petrovas
Constantinos
C
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA. petrovasc@mail.nih.gov
Chaon
Benjamin
B
Ambrozak
David R
DR
Price
David A
DA
Melenhorst
J Joseph
JJ
Hill
Brenna J
BJ
Geldmacher
Christof
C
Casazza
Joseph P
JP
Chattopadhyay
Pratip K
PK
Roederer
Mario
M
Douek
Daniel C
DC
Mueller
Yvonne M
YM
Jacobson
Jeffrey M
JM
Kulkarni
Viraj
V
Felber
Barbara K
BK
Pavlakis
George N
GN
Katsikis
Peter D
PD
Koup
Richard A
RA
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
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D018959:CD57 Antigens; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D019014:fas Receptor