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

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    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 1 2012

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    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    Zhou, Y., Callendret, B., Xu, D., Brasky, K. M., Feng, Z., Hensley, L. L., Guedj, J., Perelson, A. S., Lemon, S. M., Lanford, R. E., & Walker, C. M. (2012). Dominance of the CD4+ T helper cell response during acute resolving hepatitis a virus infection. Journal of Experimental Medicine, 209(8), 1481-1492. https://doi.org/10.1084/jem.20111906