Studies on function of HBV antigen-pulsed dendritic cells from patients with HBV-associated hepatocellular carcinoma / 解放军医学杂志

ABSTRACT

Objective To investigate the characteristics of HBsAg and HBcAg in combination pulsed monocyte-derived DCs(MoDC) derived from patients with HBV-associated hepatocellular carcinoma(HCC).Methods MoDCs were generated from 20 HBV-associated HCC patients,and pulsed with recombinant human serum albumin(rHSA)as conDC(control DC),or pulsed with HBsAg andHBcAg in combination as scDC.Phenotypic patterns of MoDCs were characterized by flow cytometry,and the levels of cytokines releasedby MoDCs were analyzed by ELISA,and frequencies of IFN-γ-producing antigen-specific autologous T cells were measured by Elispotassay.HBV-specific CD8 T cells proliferation was determined by pentamer staining.Results 1.The levels of MHC and costimulatorymolecules expressed on scDC were significantly higher than those on immature MoDC(imaDC)in two groups,and the levels of MHC andcostimulatory molecules expressed on imaDC,conDC and scDC in HBsAg+,anti-HBe+,anti-HBc+patients(1-4-5 positive group)were significantly higher than those in HBsAg+,anti-HBc+patients(1-5 positive group);2.The levels of IL-12 and IL-10 produced byscDC were higher than those produced by imaDC and conDC in both groups,and the levels of IL-12 produced by imaDC,conDC and scDCin 1-4-5 positive group were higher than those in 1-5 positive group.3.The frequencies of IFN-γ-producing T cells induced by scDC werehigher than those by conDC in 1-4-5 positive group.4.scDCs from 4 cases of HLA-A2+patients in 1-4-5 positive group could induceautologous T cells to generate HBVcore18-27-specific CD8 T cells.Condusions HBsAg and HBcAg pulse in combination couldsubstantially reverse the impaired function of MoDCs in HBv-associated HCC patients,and boost MoDC to induce HBV-specific T cellsresponse,especially in HBsAg+,anti-HBe+ and anti-HBe+ patients.