title: Activation of Th1 immunity is a common immune mechanism for the successful treatment of hepatitis B and C: tetramer assay and therapeutic implications.
abstract: Both chronic hepatitis B and C virus (HBV and HCV) infections respond ineffectively to current antiviral therapies. Recent studies have suggested that treatment outcomes may depend on the development of type 1 T helper (Th1) and Th2 cell responses. Specifically, activation of Th1 immunity may play a major role in successfully treating hepatitis B and C. This model was revisited herein by evaluating immune responses in 36 HBV and 40 HCV patients with or without treatment, in an attempt to find a common immune mechanism for successful treatment. The immune responses in all examined cases were studied by peripheral blood mononuclear cell (PBMC) proliferation and cytokine responses to viral antigens, cytotoxic T lymphocyte (CTL) responses, enzyme-linked immunospot (ELISPOT) assay, and tetramer staining of virus-specific CD8+ T cells. The overall results revealed that all responders among both HBV- and HCV-infected cases displayed significantly higher PBMC proliferation to viral antigens with a predominant Th1 cytokine profile. Furthermore, the Th1-dominant responses were associated with significant enhancement of CTL activities and were correlated with ELISPOT data, while non-responders responded more weakly. During therapy, the numbers of tetramer-staining, virus-specific CD8+ T cells showed greater increases in responders than in non-responders (p = 0.001). The frequencies determined by the tetramer assay were approximately 200-fold higher than data estimated by limiting-dilution analysis. In conclusion, activation of Th1 immunity accompanied by enhancement of CTL activity during therapy is a common immune mechanism for successfully treating hepatitis B and C, and therefore may have important therapeutic implications.
authors.affiliation: Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan. sltsai@mail.chimei.org.tw
authors.forename: Sun-Lung
authors.initials: SL
authors.lastname: Tsai
authors.forename: I-Shyan
authors.initials: IS
authors.lastname: Sheen
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Chien
authors.forename: Chia-Min
authors.initials: CM
authors.lastname: Chu
authors.forename: Hsiu-Chu
authors.initials: HC
authors.lastname: Huang
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Chuang
authors.forename: Tzong-Hsien
authors.initials: TH
authors.lastname: Lee
authors.forename: Shuen-Kuei
authors.initials: SK
authors.lastname: Liao
authors.forename: Chen-Lung
authors.initials: CL
authors.lastname: Lin
authors.forename: George C
authors.initials: GC
authors.lastname: Kuo
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D000998:Antiviral Agents; D016207:Cytokines; D000939:Epitopes