美国埃默里大学医学院Rafick P. Sekaly团队近期取得重要工作进展，他们研究提出，IL-10和PD-1双重阻断可在分析性治疗中断后控制SIV病毒反弹。相关研究成果2024年9月12日在线发表于《自然—免疫学》杂志上。

据介绍，抗逆转录病毒治疗（ART）期间，人类免疫缺陷病毒（HIV）的持续存在与血浆白细胞介素-10（IL-10）水平和PD-1表达的升高有关。

研究人员假设IL-10和PD-1阻断能控制分析治疗中断（ATI）后病毒反弹。28只经ART治疗的猿猴免疫缺陷病毒（SIV）mac₂₃₉感染的恒河猴（RM）接受了抗IL-10、抗IL-10加抗PD-1（组合）或载体治疗。在引入免疫疗法12周后，ART中断。

在ATI后超过24周的10个联合治疗RM中，有9个观察到病毒反弹的持久控制。ATI前炎性细胞因子的诱导、淋巴结中效应CD8⁺ T细胞的增殖以及CD4⁺ T细胞中BCL-2表达的降低预示着病毒反弹的控制。ATI后24周，较低的病毒载量与联合治疗RM的血液和淋巴结中表达TCF-1的记忆T细胞以及SIV特异性CD4⁺和CD8⁺T细胞的频率较高有关。

总之，这一研究为停止ART后实现HIV及SIV的长期控制提供了参考。

附：英文原文

Title: Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption

Author: Pereira Ribeiro, Susan, Strongin, Zachary, Soudeyns, Hugo, ten-Caten, Felipe, Ghneim, Khader, Pacheco Sanchez, Gabriela, Xavier de Medeiros, Giuliana, Del Rio Estrada, Perla Mariana, Pelletier, Adam-Nicolas, Hoang, Timothy, Nguyen, Kevin, Harper, Justin, Jean, Sherrie, Wallace, Chelsea, Balderas, Robert, Lifson, Jeffrey D., Raghunathan, Gopalan, Rimmer, Eric, Pastuskova, Cinthia, Wu, Guoxin, Micci, Luca, Ribeiro, Ruy M., Chan, Chi Ngai, Estes, Jacob D., Silvestri, Guido, Gorman, Daniel M., Howell, Bonnie J., Hazuda, Daria J., Paiardini, Mirko, Sekaly, Rafick P.

Issue&Volume: 2024-09-12

Abstract: Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac239-infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8+ T cells in lymph nodes and reduced expression of BCL-2 in CD4+ T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4+ and CD8+ T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART.

DOI: 10.1038/s41590-024-01952-4

Source: https://www.nature.com/articles/s41590-024-01952-4