期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：33
DOI：10.1073/pnas.2202148119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Anti-viral CD8 T cells express high levels of the co-inhibitory receptor programmed death-1 (PD-1) during chronic HIV and Simian immunodeficiency virus (SIV) infections and in vivo PD-1 blockade during chronic SIV infection restores CD8 T-cell function and improves viral control. However, it is important to define at what stage of chronic infection PD-1 blockade provides the most therapeutic benefit. In this report, we show a short-term PD-1 blockade administered 4 weeks after anti-retroviral therapy interruption provides substantial therapeutic benefit by improving the function of anti-viral CD8 T-cell immunity and rapidly controlling viremia.
Programmed death-1 (PD-1) blockade during chronic Simian immunodeficiency virus (SIV) infection results in restoration of CD8 T-cell function and enhances viral control. Here, we tested the therapeutic benefits of PD-1 blockade administered soon after anti-retrovial therapy (ART) interruption (ATI) by treating SIV-infected and ART-suppressed macaques with either an anti-PD-1 antibody (
n = 7) or saline (
n = 4) at 4 wk after ATI. Following ATI, the plasma viremia increased rapidly in all animals, and the frequency of SIV-specific CD8 T cells also increased in some animals. PD-1 blockade post ATI resulted in higher proliferation of total memory CD8 and CD4 T cells and natural killer cells. PD-1 blockade also resulted in higher proliferation of SIV-specific CD8 T cells and promoted their differentiation toward better functional quality. Importantly, four out of the seven anti-PD-1 antibody-treated animals showed a rapid decline in plasma viremia by 100- to 2300-fold and this was observed only in animals that showed measurable SIV-specific CD8 T cells post PD-1 blockade. These results demonstrate that PD-1 blockade following ATI can significantly improve the function of anti-viral CD8 T cells and enhance viral control and strongly suggests its potential synergy with other immunotherapies that induce functional CD8 T-cell response under ART. These results have important implications for HIV cure research.
