Dominance of the CD4(+) T helper cell response during acute resolving hepatitis A virus infection.
J Exp Med
; 209(8): 1481-92, 2012 Jul 30.
Article
en En
| MEDLINE
| ID: mdl-22753925
ABSTRACT
Hepatitis A virus (HAV) infection typically resolves within 4-7 wk but symptomatic relapse occurs in up to 20% of cases. Immune mechanisms that terminate acute HAV infection, and prevent a relapse of virus replication and liver disease, are unknown. Here, patterns of T cell immunity, virus replication, and hepatocellular injury were studied in two HAV-infected chimpanzees. HAV-specific CD8(+) T cells were either not detected in the blood or failed to display effector function until after viremia and hepatitis began to subside. The function of CD8(+) T cells improved slowly as the cells acquired a memory phenotype but was largely restricted to production of IFN-γ. In contrast, CD4(+) T cells produced multiple cytokines when viremia first declined. Moreover, only CD4(+) T cells responded during a transient resurgence of fecal HAV shedding. This helper response then contracted slowly over several months as HAV genomes were eliminated from liver. The findings indicate a dominant role for CD4(+) T cells in the termination of HAV infection and, possibly, surveillance of an intrahepatic reservoir of HAV genomes that decays slowly. Rapid contraction or failure to sustain such a CD4(+) T cell response after resolution of symptoms could increase the risk of relapsing hepatitis A.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T Colaboradores-Inductores
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Virus de la Hepatitis A
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Hepatitis A
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos