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

Author:

Petrovas Constantinos1,Casazza Joseph P.1,Brenchley Jason M.2,Price David A.23,Gostick Emma3,Adams William C.1,Precopio Melissa L.1,Schacker Timothy4,Roederer Mario5,Douek Daniel C.2,Koup Richard A.1

Affiliation:

1. Immunology Laboratory

2. Human Immunology Section,

3. Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK

4. Department of Medicine, University of Minnesota, Minneapolis, MN 55455

5. ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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