PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors

JY Zhang, Z Zhang, X Wang, JL Fu… - Blood, The Journal …, 2007 - ashpublications.org
JY Zhang, Z Zhang, X Wang, JL Fu, J Yao, Y Jiao, L Chen, H Zhang, J Wei, L Jin, M Shi…
Blood, The Journal of the American Society of Hematology, 2007ashpublications.org
The immunoreceptor PD-1 is significantly up-regulated on exhausted CD8+ T cells during
chronic viral infections such as HIV-1. However, it remains unknown whether PD-1
expression on CD8+ T cells differs between typical progressors (TPs) and long-term
nonprogressors (LTNPs). In this report, we examined PD-1 expression on HIV-specific CD8+
T cells from 63 adults with chronic HIV infection. We found that LTNPs exhibited functional
HIV-specific memory CD8+ T cells with markedly lower PD-1 expression. TPs, in contrast …
Abstract
The immunoreceptor PD-1 is significantly up-regulated on exhausted CD8+ T cells during chronic viral infections such as HIV-1. However, it remains unknown whether PD-1 expression on CD8+ T cells differs between typical progressors (TPs) and long-term nonprogressors (LTNPs). In this report, we examined PD-1 expression on HIV-specific CD8+ T cells from 63 adults with chronic HIV infection. We found that LTNPs exhibited functional HIV-specific memory CD8+ T cells with markedly lower PD-1 expression. TPs, in contrast, showed significantly up-regulated PD-1 expression that was closely correlated with a reduction in CD4 T-cell number and an elevation in plasma viral load. Importantly, PD-1 up-regulation was also associated with reduced perforin and IFN-γ production, as well as decreased HIV-specific effector memory CD8+ T-cell proliferation in TPs but not LTNPs. Blocking PD-1/PD-L1 interactions efficiently restored HIV-specific CD8+ T-cell effector function and proliferation. Taken together, these findings confirm the hypothesis that high PD-1 up-regulation mediates HIV-specific CD8+ T-cell exhaustion. Blocking the PD-1/PD-L1 pathway may represent a new therapeutic option for this disease and provide more insight into immune pathogenesis in LTNPs.
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