TGF-ß blockade does not improve control of an established persistent viral infection.
Viral Immunol
; 25(3): 232-8, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-22620718
ABSTRACT
Acute resolving viral infections are often associated with a strong and multi-specific T-cell response, whereas in persistent viral infections T-cell responses are often impaired. It has been suggested that the resuscitation of the antiviral T-cell response could be a powerful tool to target persisting viruses. Several immunoregulatory pathways, such as IL-10 and TGF-ß, have been shown to be involved in the induction of T-cell exhaustion and viral persistence. In this study, we sought to investigate whether TGF-ß signaling is also relevant in the maintenance of T-cell exhaustion after viral persistence has been established, and whether blockade of TGF-ß signaling could improve control of viral replication in a mouse model of persistent virus infection. Using the LCMV clone 13 model, we analyzed the frequency, function, and phenotype of virus-specific CD4 and CD8 T cells following therapeutic TGF-ß signaling blockade. We show that in vivo blockade of the TGF-ß receptor failed to substantially enhance the antiviral T-cell response, and was insufficient to mediate a therapeutically-relevant reduction of viral titers in different tissues. Thus, although TGF-ß signaling has the ability to hamper antiviral immunity, its pharmacological blockade may not be sufficient to tackle persistent viruses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Fator de Crescimento Transformador beta
/
Linfócitos T CD8-Positivos
/
Coriomeningite Linfocítica
/
Vírus da Coriomeningite Linfocítica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Viral Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
VIROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos