Dominance of the CD4+ T helper cell response during acute resolving hepatitis a virus infection

Yan Zhou, Benoît Callendret, Dan Xu, Kathleen M. Brasky, Zongdi Feng, Lucinda L. Hensley, Jeremie Guedj, Alan S. Perelson, Stanley M. Lemon, Robert E. Lanford, Christopher M. Walker

Resultado de la investigación: Articlerevisión exhaustiva

68 Citas (Scopus)

Resumen

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 chim- panzees. 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.

Idioma originalEnglish (US)
Páginas (desde-hasta)1481-1492
Número de páginas12
PublicaciónJournal of Experimental Medicine
Volumen209
N.º8
DOI
EstadoPublished - jul. 2012
Publicado de forma externa

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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