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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1481-1492
Number of pages12
JournalJournal of Experimental Medicine
Volume209
Issue number8
DOIs
StatePublished - Jul 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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