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EARLY TRANSCRIPTIONAL DIVERGENCE MARKS VIRUS-SPECIFIC PRIMARY HUMAN CD8+ T CELLS IN CHRONIC VERSUS ACUTE INFECTION
Wolski, David et al. | Fecha del documento: 2017
Autor
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.
Afiliación
Harvard Medical School. Massachusetts General Hospital. Gastrointestinal Unit and Liver Center. Boston, MA, USA / nstitut de Recherche sur les Maladies Virales et Hépatiques. Strasbourg, France / Université de Strasbourg. Strasbourg, France..
Harvard Medical School. Massachusetts General Hospital. Gastrointestinal Unit and Liver Center. Boston, MA, USA.
Harvard Medical School. Massachusetts General Hospital. Gastrointestinal Unit and Liver Center. Boston, MA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil.
Institut de Recherche sur les Maladies Virales et Hépatiques.Strasbourg, France / Université de Strasbourg. Strasbourg, France.
Harvard Medical School. Massachusetts General Hospital. Gastrointestinal Unit and Liver Center. Boston, MA, USA.
Heinrich Heine University. University Hospital Düsseldorf. Institute of Virology. Düsseldorf, Germany.
Harvard Medical School. Massachusetts General Hospital. Gastrointestinal Unit and Liver Center. Boston, MA, USA.
Harvard Medical School. Massachusetts General Hospital. Gastrointestinal Unit and Liver Center. Boston, MA, USA.
Harvard Medical School. Massachusetts General Hospital. Gastrointestinal Unit and Liver Center. Boston, MA, USA.
Harvard Medical School. Dana-Farber Cancer Institute. Department of Pediatric Oncology. Boston, MA, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA / Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Harvard Medical School. Massachusetts General Hospital. Gastrointestinal Unit and Liver Center. Boston, MA, USA.
Harvard Medical School. Massachusetts General Hospital. Gastrointestinal Unit and Liver Center. Boston, MA, USA.
Heinrich Heine University. University Hospital Düsseldorf. Institute of Virology. Düsseldorf, Germany.
Harvard Medical School. Dana-Farber Cancer Institute. Department of Pediatric Oncolog. Bston, MA, USA.
Harvard Medical School. Massachusetts General Hospital. Division of Infectious Disease. Boston, MA, USA.
Institut de Recherche sur les Maladies Virales et Hépatiques. Strasbourg, France / Université de Strasbourg, Strasbourg, France / Institut Hospitalo-Universitaire. Pôle Hépato-digestif, Nouvel Hôpital Civil. Strasbourg, France.
Harvard Medical School. Massachusetts General Hospital. Gastrointestinal Unit and Liver Center. Boston, MA, USA.
Resumen en ingles
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.
Palabras clave en portugues
Imunidade Adaptativa
Vírus da hepatite B
Metabolismo
Escapo viral
Células T CD8
Ajuda de células CD4 T
análise de rede
 
Palabras clave en ingles
CD4 T cell help
CD8 T cells
T cell dysfunction
adaptive immunity
hepatitis C virus
metabolism
network analysis
nucleosome
transciptional regulation
viral scape
 
Editor
Elsevier
Referencia
WOLSKI, D. et al. Early Transcriptional Divergence Marks Virus-Specific Primary Human CD8+ T Cells in Chronic versus Acute Infection. Immunity, v.47, n.4, p.648-663, e8, Oct. 2017.
DOI
10.1016/j.immuni.2017.09.006
ISSN
1074-7613