ABSTRACT
Objective To observe the effect of interferon (IFN) λ1 on the function of peripheral blood mononuclear cell (PBMC) derived dendritic cells (DC) in adolescents with chronic hepatitis B virus (HBV) infection.Methods A total of 34 adolescent patients with chronic HBV infection including 16 cases in immune clearance phase and 18 cases in immune tolerant phase,and 10 healthy youths were enrolled in the study.PBMC from all samples were isolated and then cultured according to the following 3 groups.IFN-λ1 group:cultured with IFN-λ1 only; normal group:cultured with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and recombinant human interleukin-4 (rhIL-4); combination group:cultured with IFN-λ1,rhGM-CSF and rhIL-4.The shape of DC was observed and the phenotypic patterns of CD83,CD80,CD86 and human leucocyte antigen (HLA)-DR were characterized by flow cytometry.The levels of interleukin 12 (IL-12) and IFN-γ in the supernatant produced by DC were analyzed with enzyme-linked immunosorbent assay (ELISA).Independent-samples t test was used to compare means between two groups and one-way ANOVA was used to compare means among multiple groups.Results In the IFN-λ1 group,the shape of adherent cells showed no change after 7 days of culture.In the normal group and combination group,typical morphology of mature state DC was observed.The expressions of phenotypic patterns of CD83,CD80,CD86 and HLA-DR in DC from immune tolerant phase patients were lower than those from healthy control youths and immune clearance phase patients (F=14.82-46.32,all P＜0.01).Co-stimuation of IFN-λ1 with rhGM-CSF and rhIL-4 up-regulated the expressions of phenotypic patterns on DC.Among patients both in immune tolerant phase and immune clearance phase,the expressions of CD83,CD80,CD86 and HLA-DR in the combination group were higher than those in normal group (t=3.16-5.69,all P＜0.01).In the normal group,the levels of IL-12 and IFN-γ in culture supernatants from healthy aldolescents were (287.25 ± 19.78) pg/mL and (56.38 ± 15.27)pg/mL,respectively; those from patients in immune tolerant phase were (198.42±22.28) pg/mL and (29.36±8.45) pg/mL,respectively; those from patients in immune clearance phase were (256.12±18.43) pg/mL and (38.38±9.72) pg/mL,respectively (F=69.22 for IL-12,F=20.29 for IFN-γ,both P＜0.01).IFN-λ1 combined with rhGM-CSF and rhIL-4 significantly up-regulated the secretion of IL-12 and IFN-γ by matured DC from patients both in immune tolerant phase and immune clearance phase (t=4.69-8.55,all P＜0.01).Conclusions In adolescent patients with chronic HBV infection,the DC function is markedly impaired in those in immune tolerant phase,compared with patients in immune clearance phase and healthy youths.IFN-λ1 can promote the maturation and phenotypic pattern expression of PBMC derived DC in adolescents with chronic HBV infection both in immune tolerant phase and immune clearance phase.