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

Citations Over TimeTop 1% of 2006 papers

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.

Related Papers

• → CD4+CD25+ T regulatory cells inhibit cytotoxic activity of T CD8+ and NK lymphocytes in the direct cell-to-cell interaction(2004)217 cited
• → Cytotoxic human CD4+ T cells(2008)124 cited
• Cytotoxic T-memory cells in virus infection and the specificity of helper T cells.(1982)
• → Generation of effector cells from T cell subsets. II. Lyt 123 T cells contain the precursors for all primary cytotoxic effector cells and for cells involved in the regulation of cytotoxic responses(1980)29 cited
• → CD29 marks superior cytotoxic human T cells(2019)6 cited