title: Lentivirally overexpressed T-bet regulates T-helper cell lineage commitment             in chronic hepatitis B patients.
abstract: Chronic hepatitis B virus (HBV) infection is commonly considered to occur as a result of disturbance of the immune system. T-box expressed in T cells (T-bet) is an essential transcription factor for T helper (Th) cell differentiation and function. The aim of this study was to investigate the effect of T-bet overexpression on Th cell differentiation and the possible mechanism in chronic hepatitis B (CHB) patients. CD4+ T cells from the peripheral blood of 23 CHB patients, 8 acute hepatitis B (AHB) patients and 10 healthy controls were isolated. T-bet mRNA expression of CD4+ T cells was detected by quantitative real-time polymerase chain reaction (PCR). The T-bet DNA fragment was subcloned into the pGC-FU vector containing GFP to generate a recombinant lentiviral vector, pGC-FU-T-bet, while a no-load pGC-FU vector was used as the negative control. After transduction into CD4+ T cells from another 22 CHB patients, the induction of Th1- and Th2-type cytokines was assayed by an enzyme-linked immunosorbent assay (ELISA), and RT-PCR and western blot analysis were used to measure the mRNA and transcription levels of H2.0-like homeobox (HLX1), GATA-3 and STAT-6. T-bet mRNA expression in CD4+ T cells from AHB patients was enhanced compared with CHB patients and healthy controls. Th1-type cytokines and HLX1 expression was upregulated, while Th2-type cytokines and GATA-3 and STAT-6 expression was repressed after lentiviral introduction of T-bet. In conclusion, lentivirally overexpressed T-bet regulates Th cell lineage commitment in CHB patients, which may be mediated by regulating HLX1, GATA-3 and STAT-6 expression.
authors.affiliation: Department of Infectious Diseases, Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, PR China.
authors.forename: Xueni
authors.initials: X
authors.lastname: Liu
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Tang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Hu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D002454:Cell Differentiation; D019070:Cell Lineage; D003001:Cloning, Molecular; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C084058:HLX protein, human; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D049452:Green Fluorescent Proteins