PURPOSE OF REVIEW

The aim of this article is to understand the dual role of programmed death-1 (PD-1) as a physiological negative regulator of T cell activation and a mediator of T cell exhaustion in HIV infection.

RECENT FINDINGS

Studies in the murine lymphocytic choriomeningitis virus model showed that the inhibitory receptor PD-1 was upregulated on the surface of exhausted virus-specific CD8 T cells and mediated a reversible impairment of immune responses. Studies in HIV infection demonstrated that PD-1 was upregulated on HIV-specific CD8 and CD4 T lymphocytes and that its expression correlated with markers of disease progression, mediated a proliferative defect of these cells and increased apoptosis of virus-specific CD8 T cells. Blockade of the PD-1 pathway enhanced HIV-specific T cell responses in vitro.

SUMMARY

These observations demonstrate an unexpected level of reversibility in HIV-specific T cell impairment. Significant efforts are required to further understanding of the PD-1 pathway. It is essential to delineate when PD-1 expression is the signal of physiologic regulatory mechanisms of activated cells, a mere marker of exhausted cells or a major mediator of functional exhaustion. The respective importance of these components, which could vary according to the stage of infection, will determine the clinical potential for immunotherapeutic intervention and the risk of adverse effects.