HIV-1 Nef impairs multiple T-cell functions in antigen-specific immune response in mice.
Int Immunol
; 23(7): 433-41, 2011 Jul.
Article
de En
| MEDLINE
| ID: mdl-21642447
ABSTRACT
The viral protein Nef is a key element for the progression of HIV disease. Previous in vitro studies suggested that Nef expression in T-cell lines enhanced TCR signaling pathways upon stimulation with TCR cross-linking, leading to the proposal that Nef lowers the threshold of T-cell activation, thus increasing susceptibility to viral replication in immune response. Likewise, the in vivo effects of Nef transgenic mouse models supported T-cell hyperresponse by Nef. However, the interpretation is complicated by Nef expression early in the development of T cells in these animal models. Here, we analyzed the consequence of Nef expression in ovalbumin-specific/CD4(+) peripheral T cells by using a novel mouse model and demonstrate that Nef inhibits antigen-specific T-cell proliferation and multiple functions required for immune response in vivo, which includes T-cell helper activity for the primary and memory B-cell response. However, Nef does not completely abrogate T-cell activity, as defined by low levels of cytokine production, which may afford the virus a replicative advantage. These results support a model, in which Nef expression does not cause T-cell hyperresponse in immune reaction, but instead reduces the T-cell activity, that may contribute to a low level of virus spread without viral cytopathic effects.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lymphocytes T
/
Antigènes du VIH
/
VIH-1 (Virus de l'Immunodéficience Humaine de type 1)
/
Produits du gène nef du virus de l'immunodéficience humaine
/
Immunité acquise
Limites:
Animals
/
Humans
Langue:
En
Journal:
Int Immunol
Sujet du journal:
ALERGIA E IMUNOLOGIA
Année:
2011
Type de document:
Article
Pays d'affiliation:
Japon