HCV-specific CD4+T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules
HCV-specific CD4+T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules
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DOI：
10.1038/s41598-019-47024-8
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发表时间：
2019-07-23
影响因子：
4.6
通讯作者：
Wiesch, Julian Schulze Zur
中科院分区：
文献类型：
--
作者：
Ackermann, Christin;Smits, Maike;Wiesch, Julian Schulze Zur
抑制性和活化性T细胞受体网络的联合调节可能是慢性HCV感染发展的关键步骤。用患有急性、慢性和自发消退的HCV感染的患者队列的基线和纵向PBMC样品进行离体HCV MHC I + II类四聚体染色和珠富集，以评估HCV特异性CD 4 + T细胞的共抑制分子TIGIT连同PD-1、BTLA、Tim-3以及0X 40和CD 226（DNAM-1）的表达模式，以及HCV特异性CD 8 + T细胞的患者亚群。作为主要结果，我们发现与自发消退的HCV感染患者相比，在急性和慢性HCV感染期间HCV特异性CD 4 + T细胞上TIGIT+ PD-1+的表达水平更高（p <0.0001）。相反，在慢性感染期间，HCV特异性CD 4 + T细胞上TIGIT的互补共刺激受体CD 226（DNAM-1）的表达显着降低。急、慢性感染时HCV特异性CD 4 + T细胞的主要表型为TIGIT+、PD-1+、BTLA+、Tim-3-。这项综合表型研究证实了TIGIT与PD-1一起作为功能失调的HCV特异性CD 4 + T细胞的区分标志物。
The combined regulation of a network of inhibitory and activating T cell receptors may be a critical step in the development of chronic HCV infection. Ex vivo HCV MHC class I + II tetramer staining and bead-enrichment was performed with baseline and longitudinal PBMC samples of a cohort of patients with acute, chronic and spontaneously resolved HCV infection to assess the expression pattern of the co-inhibitory molecule TIGIT together with PD-1, BTLA, Tim-3, as well as OX40 and CD226 (DNAM-1) of HCV-specific CD4+ T cells, and in a subset of patients of HCV-specific CD8+ T cells. As the main result, we found a higher expression level of TIGIT+ PD-1+ on HCV-specific CD4+ T cells during acute and chronic HCV infection compared to patients with spontaneously resolved HCV infection (p < 0,0001). Conversely, expression of the complementary co-stimulatory receptor of TIGIT, CD226 (DNAM-1) was significantly decreased on HCV-specific CD4+ T cells during chronic infection. The predominant phenotype of HCV-specific CD4+ T cells during acute and chronic infection was TIGIT+, PD-1+, BTLA+, Tim-3-. This comprehensive phenotypic study confirms TIGIT together with PD-1 as a discriminatory marker of dysfunctional HCV-specific CD4+ T cells.