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

By C. Petrovas, J. Casazza, J. Brenchley, D. Price, E. Gostick, W. Adams, M. Precopio, T. Schacker, Mario Roederer, Daniel C. Douek and 1 more. Journal of Experimental Medicine, 2006

995 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/9a89da28db50d0f34620149ec43e800886c6be86

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. E. Wherry
2. F. Sallusto
3. W. Zou
4. Rafi Ahmed

In Immunology

1. E. Wherry
2. Rafi Ahmed
3. Lieping Chen
4. G. Freeman
5. Arlene H. Sharpe
6. W. Zou
7. V. Kuchroo
8. D. Pardoll

Citations in the corpus

• Lytic Granule Loading of CD8+ T Cells Is Required for HIV-Infected Cell Elimination Associated with Immune Control (2008, positive): “Diminished Cytotoxic Capacity of HIV-Specific CD8 T Cells of Progressors Is Reversible Recent data have suggested that disrupted HIV-specific CD8 T cell proliferation in progressors is associated with increased surface programmed death-1 (PD-1) (Day et al., 2006; Petrovas et al., 2006; Trautmann et ”
• Emerging Concepts in the Immunopathogenesis of AIDS (2009, background): “F or p er so na l u se o nl y. ANRV367-ME60-35 ARI 4 December 2008 17:13 PD-L1: ligand for programmed death–1 T cell exhaustion: functional characteristic of CTLs often seen in chronic viral infections, where CTLs proliferate, kill, and liberate cytokines poorly in response to stimulation PD-1 in re”
• The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection (2007, background): “Those observations also apply to humans; several groups have demonstrated that PD-1 expression is higher on HIV-specific T cell”
• Phenotype and function of human T lymphocyte subsets: Consensus and issues (2008, background): “T cell regulation is also dependent on antigenic stimulation, as seen with PD-1, which is upregulated on the surface of CD8 T cells undergoing activation (24), as a likely mechanism to control the proliferation and apoptosis of activated cells (51).”
• Control of peripheral T‐cell tolerance and autoimmunity via the CTLA‐4 and PD‐1 pathways (2008, result): “Similar reports for PD-1 have been demonstrated in chronic hepatitis B virus (HBV), hepatitis C virus (HCV), simian immunodeficiency virus (SIV), and lymphocytic choriomeningitis virus (LCMV) (104, 107–109).”
• CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer. (2019, background): “Several chronic infections, such as LCMV,HIV, HBV, and HCV, are associated with increased IL-10 production (147), and polymorphisms in the IL-10 promoter that result in lower IL-10 expression can lead to better control of chronic infections (148–150).”
• T cell exhaustion (2011, result): “Shortly after the initial studies in mice, studies found that the PD-1 pathway has a central role in T cell dysfunction during HIV infectio”
• Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen–specific CD8+ T cell dysfunction in melanoma patients (2010, background): “Tim-3 is a transmembrane protein constitutively expressed on Th1/Tc1 cells in mice and humans (Monney et al., 2002).”
• PD-1 and its ligands in tolerance and immunity. (2008, background): “Blocking PD1:PD-L interactions in vitro reverses the exhaustion of HIV-specific, HBV-specific (92), HCV-specific, and SIV-specific (97) CD8 and CD4 T cells and restores proliferation and cytokine production (23, 89, 90, 93).”