title: HBcAg-specific CD8 T cells play an important role in virus suppression, and acute flare-up is associated with the expansion of activated memory T cells.
abstract: We analyzed the prevalence and longitudinal fluctuation of hepatitis B virus (HBV)-specific CD8 T cells in chronic HBV infection using an HLA-A2-HBc18-27 tetramer. Thirty-five HLA-A2-positive patients with chronic HBV infection were divided into 17 HBe antigen (HBeAg)-positive and 18 anti-HBe antibody (anti-HBe)-positive patients. Five HLA-A2-positive normal subjects, five HLA-A2-negative patients with chronic HBV infection, and two HLA-A2-positive patients with acute HBV infection were included as controls. HBc18-27-specific CD8 T cells (c18-27-CD8Ts) were detected at a significantly higher prevalence in patients with anti-HBe (6/18) than in those with HBeAg (1/17), and their frequency reached 0.28% of the total CD8 T cells. The prevalence was significantly higher in patients with HBV DNA below 4.0 log genome equivalents (LGE)/ml (5/12) than in those with HBV DNA above 4.0 LGE/ml (2/23). The frequency of c18-27-CD8Ts was consistently higher in liver-infiltrating lymphocytes, ranging from 0.18 to 1.28%, than in autologous peripheral blood lymphocytes. Longitudinal analysis of patients with acute flare-up demonstrated that the elevation of alanine aminotransferase (ALT) was intimately associated with the expansion of c18-27-CD8Ts. Phenotypic analysis revealed that most c18-27-CD8Ts during acute flare-up expressed HLA-DR and CCR5, while those during low-ALT periods showed low expression. Furthermore, most liver-infiltrating c18-27-CD8Ts were positive for HLA-DR and CCR5, suggesting selective recruitment of activated c18-27-CD8Ts into the liver. In conclusion. HBV-specific CD8 T cells play an important role in the suppression of virus replication, and acute flare-up is associated with the expansion and activation of HBV-specific memory cells.
authors.affiliation: Department of Medicine and Medical Sciences, Okayama University Graduated School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shimada
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Kuroda
authors.forename: Ryo
authors.initials: R
authors.lastname: Terada
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hakoda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimomura
authors.forename: Hidenori
authors.initials: H
authors.lastname: Hata
authors.forename: Eiichi
authors.initials: E
authors.lastname: Nakayama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shiratori
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000378:metabolism; D006509:Hepatitis B / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008099:Liver / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019713:Receptors, CCR5 / Q000276:immunology; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D015789:HLA-A2 Antigen; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D019713:Receptors, CCR5; D000410:Alanine Transaminase