美国费城威斯达研究所（The Wistar Institute）的科学家发现了人体免疫系统杀伤性T细胞外部的多个受体，研究人员认为，可以通过选择性标靶这些细胞使其维持在对抗疾病的状态。相关论文11月30日在线发表于《自然—免疫学》（Nature Immunology）。
研究领导者、威斯达副教授E. John Wherry前不久曾参与了一项研究，发现一个受体与T细胞的关闭有关。这一次，他和研究小组发现另外6个受体也能限制或负调节免疫应答。Wherry表示，这些受体可能控制T细胞应答的不同方面。
他说：“这种对T细胞应答的控制很不寻常，它表明多个抑制受体的共同表达造成了失效的T细胞上发生的负调节。我打赌这些受体抑制了T细胞应答的不同方面，不过最终的效果是使特定T细胞群失效。”
他说：“研究表明，我们不仅有可能极大增强抗病毒或抗肿瘤的T细胞应答，而且可能逆转T细胞失效这一过程，使T细胞继续对抗感染或疾病。这给了我们一个极大的临床机遇，T细胞有很多‘武器’可控制病毒感染，不过当T细胞失效后这些‘武器’都无效了。现在有可能使失效T细胞复苏，从而有选择地重新使用这些‘武器’。”
他表示：“现在的目标是理解受体控制的通路，之后弄清如何通过标靶特定的路径来微调失效的逆转，这些路径选择性地控制期望的T细胞反应类型。”（生物谷Bioon.com）
生物谷推荐原始出处：
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.
