加拿大蒙特利尔大学和美国佛罗里达免疫和基因治疗研究所的科学家合作进行的研究发现，膜蛋白PD-1和细胞衍生因子IL-10这两种分子联手作用，影响了艾滋病病人体内的CD4T细胞发挥正常作用，从而导致患者免疫系统受损并加快了患者病情的发展。专家认为，该项新发现对研究开发新型治疗艾滋病的药物将产生重要的推动作用，相关文章发表在近日出版的《自然医学》杂志上。
联合研究项目主要负责人、蒙特利尔大学拉菲克·西卡里教授介绍说，他们的研究发现，在人体受到艾滋病病毒感染期间，从肠道释放的细菌产物使膜蛋白PD-1的含量上调，导致了细胞衍生因子IL-10的产量提高，而IL-10正是破坏免疫系统的元凶。西卡里表示，这是世界上首次发现PD-1和IL-10这两种分子可以联手工作，影响艾滋病患者体内的CD4T细胞发挥正常作用，进而损坏免疫系统，使病情加速发展。
西卡里教授认为，从研究结果可以看出，阻断IL-10和PD-1两种分子之间的相互影响和作用，以恢复艾滋病患者的免疫响应非常重要，在免疫治疗上，可以以此为方向研发药物，帮助患者重建被艾滋病病毒破坏的免疫功能。(生物谷Bioon.com)
生物谷推荐原文出处：
Nature Medicine doi:10.1038/nm.2106
Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection
Elias A Said, Franck P Dupuy, Lydie Trautmann, Yuwei Zhang, Yu Shi, Mohamed El-Far, Brenna J Hill, Alessandra Noto, Petronela Ancuta, Yoav Peretz, Simone G Fonseca, Julien Van Grevenynghe, Mohamed R Boulassel, Julie Bruneau, Naglaa H Shoukry, Jean-Pierre Routy, Daniel C Douek, Elias K Haddad & Rafick-Pierre Sekaly
Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interactions between PD-1 and programmed death ligand-1 (PD-L1) and between IL-10 and IL-10 receptor (IL-10R) results in viral clearance and improves T cell function in animal models of chronic viral infections. Here we show that high amounts of microbial products and inflammatory cytokines in the plasma of HIV-infected subjects lead to upregulation of PD-1 expression on monocytes that correlates with high plasma concentrations of IL-10. Triggering of PD-1 expressed on monocytes by PD-L1 expressed on various cell types induced IL-10 production and led to reversible CD4+ T cell dysfunction. We describe a new function for PD-1 whereby microbial products inhibit T cell expansion and function by upregulating PD-1 levels and IL-10 production by monocytes after binding of PD-1 by PD-L1.
