title: B7-H1 up-regulation on myeloid dendritic cells significantly suppresses T cell immune function in patients with chronic hepatitis B.
abstract: Although dysfunctional dendritic cells contribute to inadequate adaptive immunity in chronic hepatitis B (CHB), underlying molecular mechanisms remain largely undefined. In this study, we examined B7-H1 expression on circulating myeloid dendritic cells (mDCs) in 46 CHB patients, 10 autoimmune hepatitis patients, and 10 healthy subjects as control. We found that B7-H1 expression is significantly up-regulated on circulating mDCs of CHB and autoimmune hepatitis patients compared with healthy individuals. The B7-H1 up-regulation was significantly correlated with an elevation of serum alanine aminotransaminase levels and plasma viral load. In addition, in vitro, both IFN-alpha and IFN-gamma could strongly stimulate mDCs to express B7-H1. More importantly, elevated B7-H1 expression is also closely associated with the suppression of T cell immune function. In vitro blockade of B7-H1 signaling could not only down-regulate IL-10 and up-regulate IL-12 production by mDCs, but also enhance mDC-mediated allostimulatory capacity and cytokine production of T cells. Blockade of B7-H1 signaling could improve hepatitis B c Ag-pulsed monocyte-derived DC-induced IFN-gamma production by autologous hepatitis B virus-specific T cells. These new findings suggested that chronic inflammation may contribute to B7-H1 up-regulation on mDCs in CHB patients, which potentially cause defective hepatitis B virus-specific T cell function and viral persistence. Our findings further support the notion that the blockade of B7-H1 may represent a novel therapeutic approach for this disease.
authors.affiliation: Research Center of Biological Therapy, Beijing 302 Hospital, and Center for Infection and Immunity, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, China.
authors.forename: Liangen
authors.initials: L
authors.lastname: Chen
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chen
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Shengdian
authors.initials: S
authors.lastname: Wang
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D060890:B7-H1 Antigen; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019693:Hepatitis, Autoimmune / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human