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

• Published in: The Journal of experimental medicine Vol. 203; no. 10; pp. 2281 - 2292
• Main 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
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 02.10.2006
• Subjects: Antigens, CD - immunology; Antigens, CD - metabolism; Apoptosis - immunology; Apoptosis Regulatory Proteins - immunology; Apoptosis Regulatory Proteins - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell Survival; Flow Cytometry; HIV Infections - immunology; Humans; Programmed Cell Death 1 Receptor
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20061496

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.