用PD-1阻断方法治疗HIV感染
发布日期：2009-03-17 10:28 文章来源：<a href='http://www.dxy.cn'>丁香园</a>
关键词： 点击次数：
PD-1（程序性死亡-1）是B7/CD28家族的一个免疫受体分子，抑制对慢性病毒感染的免疫反应。
研究表明，PD-1阻断能提高被SIV感染的猕猴的 抗病毒免疫反应，而不会产生副作用。这种治疗方法（采用一种对人PD-1有特异性的抗体）还能延长存活时间。PD-1阻断在没有抗逆转录病毒药物的情况下 是有效的，这说明，一种类似的治疗方法对于HIV/AIDS患者可能也是有效的，也许还可结合药物治疗或疫苗治疗来进行。
Nature 458 , 206-210 (12 March 2009) | doi :10.1038/nature07662 ; Received 14 October 2008; Accepted 21 November 2008; Published online 10 December 2008
Enhancing SIV-specific immunity in vivo by PD-1 blockade
Vijayakumar Velu 1 , 2 , 6 , Kehmia Titanji 1 , 2 , 6 , Baogong Zhu 3 , 4 , Sajid Husain 1 , 2 , Annette Pladevega 1 , 2 , Lilin Lai 1 , 2 , Thomas H. Vanderford 5 , Lakshmi Chennareddi 1 , 2 , Guido Silvestri 5 , Gordon J. Freeman 3 , 4 , Rafi Ahmed 1 & Rama Rao Amara 1 , 2
1. Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA
2. Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
4. Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
5. University of Pennsylvania School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
6. These authors contributed equally to this work.
Chronic immunodeficiency virus infections are characterized by dysfunctional cellular and humoral antiviral immune responses . As such, immune modulatory therapies that enhance and/or restore the function of virus-specific immunity may protect from disease progression. Here we investigate the safety and immune restoration potential of blockade of the co-inhibitory receptor programmed death 1 (PD-1) during chronic simian immunodeficiency virus (SIV) infection in macaques. We demonstrate that PD-1 blockade using an antibody to PD-1 is well tolerated and results in rapid expansion of virus-specific CD8 T cells with improved functional quality. This enhanced T-cell immunity was seen in the blood and also in the gut, a major reservoir of SIV infection. PD-1 blockade also resulted in proliferation of memory B cells and increases in SIV envelope-specific antibody. These improved immune responses were associated with significant reductions in plasma viral load and also prolonged the survival of SIV-infected macaques. Blockade was effective during the early (week 10) as well as late ( week 90) phases of chronic infection even under conditions of severe lymphopenia. These results demonstrate enhancement of both cellular and humoral immune responses during a pathogenic immunodeficiency virus infection by blocking a single inhibitory pathway and identify a novel therapeutic approach for control of human immunodeficiency virus infections.
Full text ：http://www.nature.com/nature/journal/v458/n7235/full/nature07662.html
Download PDF ：http://www.nature.com/nature/journal/v458/n7235/pdf/nature07662.pdf
编辑: xiaoyan 作者:丁香园通讯员