Wolski David, Foote Peter K, Chen Diana Y, Lewis-Ximenez Lia L, Fauvelle Catherine, Aneja Jasneet, Walker Andreas, Tonnerre Pierre, Torres-Cornejo Almudena, Kvistad Daniel, Imam Sabrina, Waring Michael T, Tully Damien C, Allen Todd M, Chung Raymond T, Timm Jörg, Haining W Nicholas, Kim Arthur Y, Baumert Thomas F, Lauer Georg M
Gastrointestinal Unit and Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg 67000, France; Université de Strasbourg, Strasbourg 67081, France.
Gastrointestinal Unit and Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Immunity. 2017 Oct 17;47(4):648-663.e8. doi: 10.1016/j.immuni.2017.09.006.
Distinct molecular pathways govern the differentiation of CD8 effector T cells into memory or exhausted T cells during acute and chronic viral infection, but these are not well studied in humans. Here, we employed an integrative systems immunology approach to identify transcriptional commonalities and differences between virus-specific CD8 T cells from patients with persistent and spontaneously resolving hepatitis C virus (HCV) infection during the acute phase. We observed dysregulation of metabolic processes during early persistent infection that was linked to changes in expression of genes related to nucleosomal regulation of transcription, T cell differentiation, and the inflammatory response and correlated with subject age, sex, and the presence of HCV-specific CD4 T cell populations. These early changes in HCV-specific CD8 T cell transcription preceded the overt establishment of T cell exhaustion, making this signature a prime target in the search for the regulatory origins of T cell dysfunction in chronic viral infection.
在急性和慢性病毒感染期间，不同的分子途径控制着CD8效应T细胞分化为记忆性或耗竭性T细胞，但在人类中对这些途径的研究并不充分。在这里，我们采用综合系统免疫学方法，来确定急性期持续性和自发清除丙型肝炎病毒（HCV）感染患者的病毒特异性CD8 T细胞之间转录的共性和差异。我们观察到早期持续性感染期间代谢过程的失调，这与转录的核小体调节、T细胞分化和炎症反应相关基因的表达变化有关，并与受试者的年龄、性别以及HCV特异性CD4 T细胞群体的存在相关。HCV特异性CD8 T细胞转录的这些早期变化先于T细胞耗竭的明显确立，使得这一特征成为寻找慢性病毒感染中T细胞功能障碍调节起源的主要靶点。
