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

    Research output: Contribution to journalArticlepeer-review

    56 Scopus citations


    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
    Issue number8
    StatePublished - Jul 2012

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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