Early Transcriptional Divergence Marks Virus-Specific Primary Human CD8 T Cells in Chronic versus Acute Infection.
Fiche publication
Date publication
octobre 2017
Journal
Immunity
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas
Tous les auteurs :
Wolski D, Foote PK, Chen DY, Lewis-Ximenez LL, Fauvelle C, Aneja J, Walker A, Tonnerre P, Torres-Cornejo A, Kvistad D, Imam S, Waring MT, Tully DC, Allen TM, Chung RT, Timm J, Haining WN, Kim AY, Baumert TF, Lauer GM
Lien Pubmed
Résumé
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.
Mots clés
Acute Disease, Adaptive Immunity, genetics, Adult, Aged, CD4-Positive T-Lymphocytes, immunology, CD8-Positive T-Lymphocytes, immunology, Cluster Analysis, Female, Gene Expression Profiling, methods, Gene Regulatory Networks, immunology, Genetic Variation, immunology, Hepacivirus, immunology, Hepatitis C, Chronic, genetics, Humans, Lymphocyte Activation, genetics, Male, Middle Aged, Multivariate Analysis, Time Factors, Transcription, Genetic, immunology, Young Adult
Référence
Immunity. 2017 10 17;47(4):648-663.e8