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Commentary Cell Science Reviews Vol 5 No 4 ISSN 1742-8130 |
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PD-1 blockade: A promising immunotherapy for HIV?
Bernard J.C. Macatangay 1 & Charles R. Rinaldo 2
1 Division of Infectious Diseases, University of Pittsburgh School of Medicine &
2 Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health.
Received 20th April © Cell Science 2009
The progressive loss of effector function in the setting of chronic viral infections has been associated with the upregulation of programmed death 1 (PD-1), a negative regulator of activated T cells. In HIV infection, increased levels of PD-1 expression correlate with CD8+ T cell exhaustion, which has been shown in vitro to be reversible with PD-1 blockade. Velu and colleagues recently reported the first in vivo study showing enhancement of a virus-specific immune response through PD-1 blockade using an anti-PD-1 antibody in an SIV-macaque model. Their results show an expansion of virus-specific, polyfunctional CD8+ T cells. Anti-PD1 antagonists show promise as a novel immunotherapy for HIV. However, several issues including development of autoimmunity, regulatory T cells and multiple inhibitory receptors associated with CD8+ T cell exhaustion should first be addressed to help ensure a successful response in chronic HIV infected patients.
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