PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection

C Petrovas, JP Casazza, JM Brenchley… - The Journal of …, 2006 - rupress.org
C Petrovas, JP Casazza, JM Brenchley, DA Price, E Gostick, WC Adams, ML Precopio…
The Journal of experimental medicine, 2006rupress.org
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 …
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.
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