Sun Haihua, Bi Lijuan, Zhou Junying, Zhou Dongfang, Liu Yinghui, Jin Guohua, Yan Wenzhao
Department of Infectious Diseases, Third Hospital of Hebei Medical University Shijiazhuang 050051, China.
Int J Clin Exp Pathol. 2015 Feb 1;8(2):1743-51. eCollection 2015.
The exact immunology pathogenesis of hepatitis B virus (HBV) infection remains unclear currently. The dendritic cells (DCs) dysfunction is evident in adolescents with chronic HBV infection in the immune tolerant phase. DCs, as the most efficient professional antigen-presenting cells (APCs), possess the strongest antigen presenting the effect in the body and can stimulate the initial T cell activation and proliferation, depending on their stage of maturation. The recently classified type III interferon group, interferon-λ1 (IL-29), interferon-λ2 (IL-28A), and interferon-λ3 (IL-28B) displays immunomodulatory and antiviral activity. In the current study, we describe a way to stimulate the DCs maturation. As a result, IFN-λ1 combined with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and recombinant human interleukin-4 (rhIL-4) can induce the DCs maturation and promote the costimulatory molecules such as CD80, CD83, CD86 and human leucocyte antigen DR (HLA-DR) expression in the immune tolerance and the clearance phases. This study demonstrates that the DCs function is remarkably impaired both in the immune tolerant phase and the immune clearance phase in adolescents with chronic HBV infection compared with healthy youth control. At the same time, this study has developed a theoretical basis for the application of IFN-λ1 breaking immune tolerance and improving the body's immune system to clear HBV.
目前,乙型肝炎病毒(HBV)感染的确切免疫发病机制仍不清楚。在免疫耐受期的慢性HBV感染青少年中,树突状细胞(DCs)功能障碍明显。DCs作为最有效的专职抗原呈递细胞(APCs),在体内具有最强的抗原呈递作用,并且根据其成熟阶段能够刺激初始T细胞的活化和增殖。最近分类的III型干扰素组,即干扰素-λ1(IL-29)、干扰素-λ2(IL-28A)和干扰素-λ3(IL-28B)具有免疫调节和抗病毒活性。在本研究中,我们描述了一种刺激DCs成熟的方法。结果表明,IFN-λ1联合重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)和重组人白细胞介素-4(rhIL-4)可诱导DCs成熟,并促进免疫耐受期和清除期共刺激分子如CD80、CD83、CD86和人类白细胞抗原DR(HLA-DR)的表达。本研究表明,与健康青年对照组相比,慢性HBV感染青少年在免疫耐受期和免疫清除期的DCs功能均显著受损。同时,本研究为应用IFN-λ1打破免疫耐受和改善机体免疫系统清除HBV奠定了理论基础。