CTL公司*
淋巴细胞性脉络膜脑膜炎
免疫学
病毒
封锁
细胞毒性T细胞
免疫系统
慢性感染
生物
医学
病毒学
受体
CD8型
内科学
生物化学
体外
作者
Jonathan Chen,Curtis J. Perry,Yao‐Chen Tsui,Matthew Staron,Ian A. Parish,Claudia X. Dominguez,Daniel W. Rosenberg,Susan M. Kaech
出处
期刊:Nature Medicine
[Springer Nature]
日期:2015-03-23
卷期号:21 (4): 327-334
被引量:130
摘要
Susan Kaech and colleagues report that in chronic viral infection, prostaglandin E2 and PD-1 signaling suppressed the function and survival of cytotoxic T cells. More than 10% of the world's population is chronically infected with HIV, hepatitis C virus (HCV) or hepatitis B virus (HBV), all of which can cause severe disease and death. These viruses persist in part because continuous antigenic stimulation causes the deterioration of virus-specific cytotoxic T lymphocyte (CTL) function and survival. Additionally, antiviral CTLs autonomously suppress their responses to limit immunopathology by upregulating inhibitory receptors such as programmed cell death 1 (PD-1). Identification and blockade of the pathways that induce CTL dysfunction may facilitate the clearance of chronic viral infections. We found that the prostaglandin E2 (PGE2) receptors EP2 and EP4 were upregulated on virus-specific CTLs during chronic lymphocytic choriomeningitis virus (LCMV) infection and suppressed CTL survival and function. We show that the combined blockade of PGE2 and PD-1 signaling was therapeutic in terms of improving viral control and augmenting the numbers of functional virus-specific CTLs. Thus, PGE2 inhibition is both an independent candidate therapeutic target and a promising adjunct therapy to PD-1 blockade for the treatment of HIV and other chronic viral infections.
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