研究人員在《自然—免疫學(xué)》期刊上指出,，他們發(fā)現(xiàn)了免疫系統(tǒng)被耗盡的途徑,，以及讓它們恢復(fù)活力的方法,。
病毒感染會引起普通感冒或流感，因此會觸發(fā)免疫系統(tǒng),。一種名為“CD8+T”特定的殺手T細胞能進攻感染細胞的病毒，摧毀病毒的防御系統(tǒng),，患者通常在幾天內(nèi)就痊愈了。然而,，像肺炎病毒和人體免疫缺損病毒等,，會引發(fā)相當(dāng)頑固的感染，導(dǎo)致免疫系統(tǒng)精疲力竭而喪失功能,，最終疾病無法治愈,。
John Wherry和同事認真研究了這種免疫無反應(yīng)機制。他們發(fā)現(xiàn),，通過讓免疫細胞表達多種抑制受體，小鼠體內(nèi)的慢性感染會讓免疫細胞無能為力,。這些受體的表達不是隨機的,，而是以一種特定的秩序進行,，越嚴重的感染會觸發(fā)更多種類的抑制受體的表達,。通過阻斷多種抑制受體,，研究小組恢復(fù)了CD8+T細胞的殺敵能力。
他們計劃通過進一步的研究,，確定阻斷抑制受體是否真能恢復(fù)慢性感染患者體內(nèi)被耗盡的T細胞的功能,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Immunology,，doi:10.1038/ni.1679,，Shawn D Blackburn，E John Wherry
Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection
Shawn D Blackburn1, Haina Shin1, W Nicholas Haining2,3, Tao Zou1, Creg J Workman6, Antonio Polley1, Michael R Betts5, Gordon J Freeman4, Dario A A Vignali6 & E John Wherry1
Abstract
T cell exhaustion often occurs during chronic infection and prevents optimal viral control. The molecular pathways involved in T cell exhaustion remain poorly understood. Here we show that exhausted CD8+ T cells are subject to complex layers of negative regulation resulting from the coexpression of multiple inhibitory receptors. Exhausted CD8+ T cells expressed up to seven inhibitory receptors. Coexpression of multiple distinct inhibitory receptors was associated with greater T cell exhaustion and more severe infection. Regulation of T cell exhaustion by various inhibitory pathways was nonredundant, as blockade of the T cell inhibitory receptors PD-1 and LAG-3 simultaneously and synergistically improved T cell responses and diminished viral load in vivo. Thus, CD8+ T cell responses during chronic viral infections are regulated by complex patterns of coexpressed inhibitory receptors.
1 Immunology Program and Wistar Vaccine Center, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
2 Department of Hematology/Oncology, Children's Hospital, Boston, Massachusetts, USA.
3 Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
4 Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
5 Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
6 Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
