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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

PD-1 Signaling in HIV and Chronic Viral Infection – Potential for Therapeutic Intervention?

Author(s): Q. Eichbaum

Volume 18, Issue 26, 2011

Page: [3971 - 3980] Pages: 10

DOI: 10.2174/092986711796957239

Price: $65

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.

Keywords: HIV, PD-1, signaling, T cell receptor, therapeutic intervention, vaccine


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