| Author | Tonnerre, Pierre | |
| Author | Wolski, David | |
| Author | Subudhi, Sonu | |
| Author | Al-Jabban, Jihad | |
| Author | Hoogeveen, Ruben C. | |
| Author | Damasio, Marcos | |
| Author | Drescher, Hannah K. | |
| Author | Bartsch, Lea M. | |
| Author | Tully, Damien C. | |
| Author | Sen, Debattama R. | |
| Author | Bean, David J. | |
| Author | Brown, Joelle | |
| Author | Torres-Cornejo, Almudena | |
| Author | Robidoux, Maxwell | |
| Author | Kvistad, Daniel | |
| Author | Alatrakchi, Nadia | |
| Author | Cui, Ang | |
| Author | Lieb, David | |
| Author | Cheney, James A. | |
| Author | Gustafson, Jenna | |
| Author | Lewis-Ximenez, Lia L. | |
| Author | Massenet-Regad, Lucile | |
| Author | Eisenhaure, Thomas | |
| Author | Aneja, Jasneet | |
| Author | Haining, W. Nicholas | |
| Author | Chung, Raymond T. | |
| Author | Hacohen, Nir | |
| Author | Allen, Todd M. | |
| Author | Kim, Arthur Y. | |
| Author | Lauer, Georg M. | |
| Access date | 2021-11-07T15:47:07Z | |
| Available date | 2021-11-07T15:47:07Z | |
| Document date | 2021 | |
| Citation | TONNERRE, Pierre et al. Differentiation of exhausted CD8 T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory. bioRxiv preprint, p. 1-49, Apr. 2021. | |
| URI | https://www.arca.fiocruz.br/handle/icict/49718 | |
| Language | eng | en_US |
| Publisher | bioRxiv | |
| Rights | restricted access | |
| Subject in Portuguese | Exaustão de células T | pt_BR |
| Subject in Portuguese | Recuperação imunológica | pt_BR |
| Subject in Portuguese | Infecção por HCV | pt_BR |
| Subject in Portuguese | Terapia antiviral | pt_BR |
| Title | Differentiation of exhausted CD8 T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory | en_US |
| Type | Preprint | |
| DOI | 10.1101/2021.04.03.437705 | |
| Abstract | T cell exhaustion is associated with failure to clear chronic infections and malignant cells. Defining the molecular mechanisms of T cell exhaustion and reinvigoration is essential to improving immunotherapeutic modalities. Analysis of antigen-specific CD8+ T cells before and after antigen removal in human hepatitis C virus (HCV) infection confirmed pervasive phenotypic, functional, and transcriptional differences between exhausted and memory CD8+ T cells. After viral cure, we observed broad phenotypic and transcriptional changes in clonally stable exhausted T-cell populations suggesting differentiation towards a memory-like profile. However, functionally, the cells showed little improvement and critical transcriptional regulators remained in the exhaustion state. Notably, T cells from chronic HCV infection that were exposed to antigen for shorter periods of time because of viral escape mutations were functionally and transcriptionally more similar to memory T cells from spontaneously resolved acute HCV infection. Thus, duration of T cell stimulation impacts the ability to recover from exhaustion, as antigen removal after long-term T cell exhaustion is insufficient for the development of key T cell memory characteristics. | en_US |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA / Inserm U976, Institut de Recherche Saint-Louis, Paris, France. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. | |
| Affilliation | Division of Medical Sciences, Harvard Medical School, Boston, MA, USA / Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. | |
| Affilliation | Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Broad Institute of MIT and Harvard, Cambridge, MA, USA / Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, MA, USA.. | |
| Affilliation | Broad Institute of MIT and Harvard, Cambridge, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Inserm U976, Institut de Recherche Saint-Louis, Paris, France. | |
| Affilliation | Broad Institute of MIT and Harvard, Cambridge, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA / Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Medical Sciences, Harvard Medical School, Boston, MA, USA / Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Broad Institute of MIT and Harvard, Cambridge, MA, USA / Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.. | |
| Affilliation | Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. | |
| Affilliation | Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Affilliation | Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. | |
| Subject | T cell exhaustion | en_US |
| Subject | Immunological recovery | en_US |
| Subject | HCV infection | en_US |
| Subject | Antiviral therapy | en_US |
| Publication status | Não publicado. | |
