美國費(fèi)城威斯達(dá)研究所（The Wistar Institute）的科學(xué)家發(fā)現(xiàn)了人體免疫系統(tǒng)殺傷性T細(xì)胞外部的多個受體,，研究人員認(rèn)為,，可以通過選擇性標(biāo)靶這些細(xì)胞使其維持在對抗疾病的狀態(tài)。相關(guān)論文11月30日在線發(fā)表于《自然—免疫學(xué)》（Nature Immunology）,。
研究領(lǐng)導(dǎo)者,、威斯達(dá)副教授E. John Wherry前不久曾參與了一項(xiàng)研究，發(fā)現(xiàn)一個受體與T細(xì)胞的關(guān)閉有關(guān),。這一次,，他和研究小組發(fā)現(xiàn)另外6個受體也能限制或負(fù)調(diào)節(jié)免疫應(yīng)答。Wherry表示,，這些受體可能控制T細(xì)胞應(yīng)答的不同方面,。
他說：“這種對T細(xì)胞應(yīng)答的控制很不尋常，它表明多個抑制受體的共同表達(dá)造成了失效的T細(xì)胞上發(fā)生的負(fù)調(diào)節(jié),。我打賭這些受體抑制了T細(xì)胞應(yīng)答的不同方面,，不過最終的效果是使特定T細(xì)胞群失效。”
他說：“研究表明,，我們不僅有可能極大增強(qiáng)抗病毒或抗腫瘤的T細(xì)胞應(yīng)答，而且可能逆轉(zhuǎn)T細(xì)胞失效這一過程,，使T細(xì)胞繼續(xù)對抗感染或疾病,。這給了我們一個極大的臨床機(jī)遇，T細(xì)胞有很多‘武器’可控制病毒感染,，不過當(dāng)T細(xì)胞失效后這些‘武器’都無效了?，F(xiàn)在有可能使失效T細(xì)胞復(fù)蘇，從而有選擇地重新使用這些‘武器’。”
他表示：“現(xiàn)在的目標(biāo)是理解受體控制的通路,，之后弄清如何通過標(biāo)靶特定的路徑來微調(diào)失效的逆轉(zhuǎn),，這些路徑選擇性地控制期望的T細(xì)胞反應(yīng)類型。”（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
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.
