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- Title
PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection.
- Authors
Petrovas, Constantinos; Casazza, Joseph P; Brenchley, Jason M; Price, David A; Gostick, Emma; Adams, William C; Precopio, Melissa L; Schacker, Timothy; Roederer, Mario; Douek, Daniel C; Koup, Richard A
- Abstract
Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) T cells according to antigen specificity. Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo.
- Publication
The Journal of experimental medicine, 2006, Vol 203, Issue 10, p2281
- ISSN
0022-1007
- Publication type
Journal Article
- DOI
10.1084/jem.20061496