Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: the role of the virus.
Eur J Immunol
; 34(2): 438-46, 2004 Feb.
Article
em En
| MEDLINE
| ID: mdl-14768048
ABSTRACT
In a companion study, we showed a dichotomy between the expansion of central memory (CCR7(+)) hepatitis C virus (HCV)-specific CTL and the incomplete memory effector differentiation in patients with acute HCV infection. Indeed, effector cells were unable to perform immediate functions, despite expressing the tissue-homing phenotype of effector memory cells (CCR7(-); semi-effectors). However, since they promptly differentiated into full-effectors upon IL-2 contact, we suggested that the inhibitory effect by environmental (possibly viral) factors on IL-2 production may have a pivotal role in generating the large population of semi-effector CCR7(-)/IFN-gamma(-) CTL. In accord with this view, we report here strong evidence in support of circulating HCVcore protein (HCVcore) playing a central role in inhibiting effector CTL differentiation, but not memory CTL expansion. The regulatory HCVcore effect is related to inhibition of the signal transduction pathway instrumental for IL-2 production, supporting the evidence that IL-2 was capable both of pushing semi-effector CTL to complete their effector cell program and of restoring the HCVcore-dependent inhibitory effect. Therefore, the strength of CTL activation is dependent on the balance between the threshold of stimulatory signals and the viral interference capacities provided during priming.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Interleucina-2
/
Hepatite C
/
Linfócitos T Reguladores
/
Hepacivirus
Limite:
Adult
/
Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article