Polyfunctional type-1, -2, and -17 CD8⺠T cell responses to apoptotic self-antigens correlate with the chronic evolution of hepatitis C virus infection.
PLoS Pathog
; 8(6): e1002759, 2012.
Article
em En
| MEDLINE
| ID: mdl-22737070
ABSTRACT
Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8⺠T cell responses in various infectious diseases. We found that the emergence of a large population of autoreactive CD8⺠T effector cells specific for apoptotic T cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis C virus infection. Importantly, they endow mixed polyfunctional type-1, type-2 and type-17 responses and correlate with the chronic progression of infection. This evolution is related to the selection of autoreactive CD8⺠T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients who clear infection. These findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive CD8⺠T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2
) and the progression toward chronic disease in a human model of acute infection.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
/
Subpopulações de Linfócitos T
/
Hepatite C
/
Apoptose
/
Linfócitos T CD8-Positivos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article