title: PD-1 signaling in HIV and chronic viral infection--potential for therapeutic intervention?
abstract: Programmed death-1 (PD-1) is a negative immunoregulatory cell surface receptor molecule whose interaction with its ligands PD-L1 and PD-L2 downmodulates T-cell immune responses. Originally investigated in the context of self-tolerance, PD-1 has more recently been discovered to be upregulated on T cells of HIV-infected individuals. High levels of PD-1 on HIV-infected T cells are correlated with viral load and with a state of cellular anergy, or ' exhaustion'  that results in decreased cellular proliferation, cytotoxic function and cytokine secretion. The finding that interruption of PD-1 with its ligand PD-L1 rescues HIV-infected cells from this state of anergy or ' exhaustion'  presents the promise for therapeutic intervention. Understanding the molecular signaling pathway(s) of PD-1 may provide opportunities for therapeutic intervention, that may serve as adjunctive therapies to HIV vaccine development. Evidence to date suggests that PD-1 exerts its regulatory effect by interfering with T cell receptor signaling. While certain molecular signals in the PD-1 pathway have been identified, their precise roles and mechanisms of action remain poorly understood. This article reviews what is currently known about PD-1 signaling in human T cells, and more specifically in T cells of individuals chronically infected with certain viruses such as HIV.
authors.affiliation: 319 Light Hall, Vanderbilt University School of Medicine, Nashville, TN 37232-0242, USA. quentin.eichbaum@vanderbilt.edu
authors.forename: Q
authors.initials: Q
authors.lastname: Eichbaum
mesh_terms: D002908:Chronic Disease / Q000517:prevention & control / Q000628:therapy; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control* / Q000628:therapy; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor