生物谷報(bào)道： 治療感染類疾病以及發(fā)明疫苗面臨的最主要問題在于,，慢性感染疾病能阻止免疫T細(xì)胞的反應(yīng)能力。由Emory大學(xué)領(lǐng)導(dǎo)的研究小組最近發(fā)現(xiàn)了慢性病毒感染疾病逃脫免疫反應(yīng)的重要方式,。結(jié)果發(fā)表在最新的在線版《美國(guó)國(guó)家科學(xué)院院刊》（Proceedings of the National Academy of Science,，PNAS）上。
利用老鼠模型,，科學(xué)家發(fā)現(xiàn)一種慢性淋巴脈絡(luò)叢腦炎病毒（LCMV）攻擊一種淋巴器官中被稱為纖維原網(wǎng)狀細(xì)胞（FRC）的基質(zhì)細(xì)胞,。而急性病毒則對(duì)FRC沒有作用,。FRC為免疫細(xì)胞提供移動(dòng)和與淋巴器官（脾臟、淋巴結(jié)）中其它免疫細(xì)胞作用的三維網(wǎng)絡(luò),。FRC對(duì)于免疫反應(yīng)的發(fā)動(dòng)很重要,。科學(xué)家發(fā)現(xiàn)FRC感染的傳播將導(dǎo)致這一重要基質(zhì)細(xì)胞功能的破壞,。
去年Emory科學(xué)家Rafi Ahmed領(lǐng)導(dǎo)的小組發(fā)現(xiàn)在老鼠中,，另一種針對(duì)慢性感染的免疫反應(yīng)路徑被中斷——這是稱為PD-1的阻斷慢性LCMV反應(yīng)的路徑。
目前負(fù)責(zé)實(shí)驗(yàn)的是Ahmed實(shí)驗(yàn)室的博士后Scott N. Mueller,。小組同時(shí)還包括來自Emory移植中心和醫(yī)學(xué)院,、California大學(xué)San Francisco分校（UCSF）、Los Angeles分校（UCLA）,、哈佛醫(yī)學(xué)院,、Dana-Farber癌癥中心的科學(xué)家。 小組發(fā)現(xiàn)FRC感染或許和之前發(fā)現(xiàn)的PD-1路徑有關(guān),。PD-1的主要配合體PD-L1在FRC感染后增加了,。PD-1路徑或許會(huì)阻止CD8+T細(xì)胞和FRC之間的相互作用，防止脾臟中FRC結(jié)構(gòu)的破壞,。這能幫助病毒持續(xù)感染FRC,，造成慢性長(zhǎng)期的病毒存在。( 教育部科技發(fā)展中心)
原文鏈接：http://www.physorg.com/news109333710.html
原始出處：
Published online before print September 18, 2007, 10.1073/pnas.0702579104
PNAS | September 25, 2007 | vol. 104 | no. 39 | 15430-15435
BIOLOGICAL SCIENCES / IMMUNOLOGY
Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection
Scott N. Mueller*, Mehrdad Matloubian, Daniel M. Clemens, Arlene H. Sharpe, Gordon J. Freeman¶,||, Shivaprakash Gangappa**, Christian P. Larsen**, and Rafi Ahmed*,
*Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322; Department of Medicine, Division of Rheumatology, University of California, San Francisco, CA 94143; Department of Medicine, Division of Infectious Diseases, University of California, Los Angeles, CA 90095; Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115; ¶Department of Medical Oncology, Dana–Farber Cancer Institute, Boston, MA 02115; ||Department of Medicine, Harvard Medical School, Boston, MA 02115; and **Emory Transplant Center and Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322
Edited by James P. Allison, Memorial Sloan–Kettering Cancer Center, New York, NY, and approved August 10, 2007 (received for review March 19, 2007)
Many chronic viral infections are marked by pathogen persistence and a generalized immunosuppression. The exact mechanisms by which this occurs are still unknown. Using a mouse model of persistent lymphocytic choriomeningitis virus (LCMV) infection, we demonstrate viral targeting of fibroblastic reticular cells (FRC) in the lymphoid organs. The FRC stromal networks are critical for proper lymphoid architecture and function. High numbers of FRC were infected by LCMV clone 13, which causes a chronic infection, whereas few were infected by the acute strain, LCMV Armstrong. The function of the FRC conduit network was altered after clone 13 infection by the action of CD8+ T cells. Importantly, expression of the inhibitory programmed death ligand 1, which was up-regulated on FRC after infection, reduced early CD8+ T cell-mediated immunopathology and prevented destruction of the FRC architecture in the spleen. Together, this reveals an important tropism during a persistent viral infection. These data also suggest that the inhibitory PD-1 pathway, which likely evolved to prevent excessive immunopathology, may contribute to viral persistence in FRC during chronic infection.
immunopathology | stromal cells | viral infection
Fig. 1. Reticular pattern of virus infection in the spleen after CL-13 infection. (A) Spleens from mice infected with LCMV Armstrong (Arm) or CL-13 3 days earlier were stained for LCMV antigen, counterstained with Mayer's hematoxylin, and examined via microscopy. (B) Spleens and LN (Right) stained for ER-TR7 (green) and LCMV (red) on days 1–30 after infection. White regions indicate colocalization. [Magnification: x20 (spleen) and x10 (LN). Scale bars: 100 µm (spleen) and 400 µm (LN).]
