title: Dominance of the CD4(+) T helper cell response during acute resolving hepatitis A virus infection.
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.
authors: Center for Vaccines and Immunity, the Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA.
authors: Yan
authors: Y
authors: Zhou
authors: Benoît
authors: B
authors: Callendret
authors: Dan
authors: D
authors: Xu
authors: Kathleen M
authors: KM
authors: Brasky
authors: Zongdi
authors: Z
authors: Feng
authors: Lucinda L
authors: LL
authors: Hensley
authors: Jeremie
authors: J
authors: Guedj
authors: Alan S
authors: AS
authors: Perelson
authors: Stanley M
authors: SM
authors: Lemon
authors: Robert E
authors: RE
authors: Lanford
authors: Christopher M
authors: CM
authors: Walker
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D005260:Female; D006506:Hepatitis A / Q000276:immunology* / Q000821:virology; D030041:Hepatitis A virus / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000821:virology; D008297:Male; D002679:Pan troglodytes; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000821:virology; D014779:Virus Replication
chemical_list: D007371:Interferon-gamma