Author | Chen, Diana Y. | |
Author | Wolski, David | |
Author | Aneja, Jasneet | |
Author | Matsubara, Lyndon | |
Author | Robilotti, Brandon | |
Author | Hauck, Garrett | |
Author | Sousa, Paulo Sergio Fonseca de | |
Author | Subudhi, Sonu | |
Author | Fernandes, Carlos Augusto | |
Author | Hoogeveen, Ruben C. | |
Author | Kim, Arthur Y. | |
Author | Lewis-Ximenez, Lia | |
Author | Lauer, Georg M. | |
Access date | 2020-07-30T18:48:49Z | |
Available date | 2020-07-30T18:48:49Z | |
Document date | 2020 | |
Citation | CHEN, Diana Y. et al. Hepatitis C virus–specific CD4+ T cell phenotype and function in different infection outcomes. The Journal of Clinical Investigation, v. 130, n. 2, p. 768-773, Feb. 2020. | pt_BR |
ISSN | 0021-9738 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/42474 | |
Language | eng | pt_BR |
Publisher | American Society for Clinical Investigation | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Vírus da Hepatite C | pt_BR |
Subject in Portuguese | CD4+ específico | pt_BR |
Subject in Portuguese | Fenótipo de células T | pt_BR |
Subject in Portuguese | Infecção | pt_BR |
Title | Hepatitis C virus-specific CD4+ T cell phenotype and function in different infection outcomes | pt_BR |
Type | Article | pt_BR |
DOI | 10.1172/JCI126277 | |
Abstract | CD4+ T cell failure is a hallmark of chronic hepatitis C virus (HCV) infection. However, the mechanisms underlying the impairment and loss of virus-specific CD4+ T cells in persisting HCV infection remain unclear. Here we examined HCV-specific CD4+ T cells longitudinally during acute infection with different infection outcomes. We found that HCV-specific CD4+ T cells are characterized by expression of a narrower range of T cell inhibitory receptors compared with CD8+ T cells, with initially high expression levels of PD-1 and CTLA-4 that were associated with negative regulation of proliferation in all patients, irrespective of outcome. In addition, HCV-specific CD4+ T cells were phenotypically similar during early resolving and persistent infection and secreted similar levels of cytokines. However, upon viral control, CD4+ T cells quickly downregulated inhibitory receptors and differentiated into long-lived memory cells. In contrast, persisting viremia continued to drive T cell activation and PD-1 and CTLA-4 expression, and blocked T cell differentiation, until the cells quickly disappeared from the circulation. Our data support an important and physiological role for inhibitory receptor-mediated regulation of CD4+ T cells in early HCV infection, irrespective of outcome, with persistent HCV viremia leading to sustained upregulation of PD-1 and CTLA-4. | pt_BR |
Affilliation | Massachusetts General Hospital and Harvard Medical School, Boston. Gastrointestinal Unit. Boston, Massachusetts, USA. | pt_BR |
Affilliation | Massachusetts General Hospital and Harvard Medical School, Boston. Gastrointestinal Unit. Boston, Massachusetts, USA. | pt_BR |
Affilliation | Massachusetts General Hospital and Harvard Medical School, Boston. Gastrointestinal Unit. Boston, Massachusetts, USA / Massachusetts General Hospital and Harvard Medical School, Infectious Disease Division. Boston | pt_BR |
Affilliation | Massachusetts General Hospital and Harvard Medical School, Boston. Gastrointestinal Unit, Boston, Massachusetts, USA.. | pt_BR |
Affilliation | Massachusetts General Hospital and Harvard Medical School, Boston. Gastrointestinal Unit. Boston, Massachusetts, USA. | pt_BR |
Affilliation | Massachusetts General Hospital and Harvard Medical School, Boston. Gastrointestinal Unit. Boston, Massachusetts, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Massachusetts General Hospital and Harvard Medical School, Boston. Gastrointestinal Unit. Boston, Massachusetts, USA. | pt_BR |
Affilliation | Laboratório Central de Sáud Pública Noel Nutels. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Massachusetts General Hospital and Harvard Medical School, Boston. Gastrointestinal Unit. Boston, Massachusetts, USA. | pt_BR |
Affilliation | Massachusetts General Hospital and Harvard Medical School, Infectious Disease Division. Boston | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Infecções Virais. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Massachusetts General Hospital and Harvard Medical School, Boston. Gastrointestinal Unit. Boston, Massachusetts, USA. | pt_BR |
Subject | Hepatitis C virus | pt_BR |
Subject | CD4+ T cell phenotype | pt_BR |
Subject | Infection outcomes | pt_BR |
Subject | Phenotype | pt_BR |
e-ISSN | 1558-8238 | |