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(huì)引起普通感冒或流感,，因此會(huì)觸發(fā)免疫系統(tǒng),。一種名為“CD8+T”特定的殺手T細(xì)胞能進(jìn)攻感染細(xì)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(huì)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(wú)法治愈,。
John Wherry和同事認(rèn)真研究了這種免疫無(wú)反應(yīng)機(jī)制。他們發(fā)現(xiàn),，通過(guò)讓免疫細(xì)胞表達(dá)多種抑制受體,，小鼠體內(nèi)的慢性感染會(huì)讓免疫細(xì)胞無(wú)能為力。這些受體的表達(dá)不是隨機(jī)的,，而是以一種特定的秩序進(jìn)行,，越嚴(yán)重的感染會(huì)觸發(fā)更多種類的抑制受體的表達(dá)。通過(guò)阻斷多種抑制受體,，研究小組恢復(fù)了CD8+T細(xì)胞的殺敵能力,。
他們計(jì)劃通過(guò)進(jìn)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(xì)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.
