加拿大蒙特利爾大學(xué)和美國佛羅里達(dá)免疫和基因治療研究所的科學(xué)家合作進(jìn)行的研究發(fā)現(xiàn),，膜蛋白PD-1和細(xì)胞衍生因子IL-10這兩種分子聯(lián)手作用，影響了艾滋病病人體內(nèi)的CD4T細(xì)胞發(fā)揮正常作用,，從而導(dǎo)致患者免疫系統(tǒng)受損并加快了患者病情的發(fā)展,。專家認(rèn)為,，該項新發(fā)現(xiàn)對研究開發(fā)新型治療艾滋病的藥物將產(chǎn)生重要的推動作用，相關(guān)文章發(fā)表在近日出版的《自然醫(yī)學(xué)》雜志上,。
聯(lián)合研究項目主要負(fù)責(zé)人,、蒙特利爾大學(xué)拉菲克·西卡里教授介紹說，他們的研究發(fā)現(xiàn),，在人體受到艾滋病病毒感染期間,，從腸道釋放的細(xì)菌產(chǎn)物使膜蛋白PD-1的含量上調(diào)，導(dǎo)致了細(xì)胞衍生因子IL-10的產(chǎn)量提高,，而IL-10正是破壞免疫系統(tǒng)的元兇,。西卡里表示，這是世界上首次發(fā)現(xiàn)PD-1和IL-10這兩種分子可以聯(lián)手工作,，影響艾滋病患者體內(nèi)的CD4T細(xì)胞發(fā)揮正常作用,，進(jìn)而損壞免疫系統(tǒng),，使病情加速發(fā)展。
西卡里教授認(rèn)為,，從研究結(jié)果可以看出,，阻斷IL-10和PD-1兩種分子之間的相互影響和作用，以恢復(fù)艾滋病患者的免疫響應(yīng)非常重要,，在免疫治療上,，可以以此為方向研發(fā)藥物，幫助患者重建被艾滋病病毒破壞的免疫功能,。(生物谷Bioon.com)
生物谷推薦原文出處：
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.
