Institute of Clinical Immunology, University of Los Andes, Merida, Venezuela.
Cell Immunol. 2013 Jul-Aug;284(1-2):9-19. doi: 10.1016/j.cellimm.2013.05.008. Epub 2013 Jul 1.
Hepatitis B is considered to be a worldwide public health problem. An immunosuppressor microenvironment has been proposed to contribute to viral persistence during chronic disease. Understanding the intracellular signaling cascade in T-cells from HBV-infected patients, will contribute to unravel the mechanisms that control the development of immune response during hepatitis B. We analyze lipid rafts formation and early activation signals in chronic HBV infected patients, compared to naturally immune subjects (NIS). Patients show: (1) diminished GM1 clustering, (2) A deficient lipid rafts recruitment of CD3ζ/ZAP-70/Grb2, and (3) these proteins do not merge with GM1 within the lipid rafts. Finally, immunoprecipitation assays proved that ZAP-70 does not associate to CD3ζ. These results show for the first time, defects regarding early key events in T-cell activation, in chronically infected HBV patients, which may contribute not only to understand HBV immune tolerance, but to reveal new potential therapeutic targets to control the infection.
乙型肝炎被认为是一个全球性的公共卫生问题。有人提出免疫抑制微环境有助于慢性疾病期间病毒的持续存在。了解乙型肝炎病毒感染患者 T 细胞中的细胞内信号级联反应将有助于揭示控制乙型肝炎期间免疫反应发展的机制。我们分析了慢性 HBV 感染患者与自然免疫受试者（NIS）相比，脂筏的形成和早期激活信号。患者表现出：（1）GM1 聚集减少，（2）CD3ζ/ZAP-70/Grb2 的脂筏募集减少，（3）这些蛋白不在脂筏内与 GM1 融合。最后，免疫沉淀测定证明 ZAP-70 不与 CD3ζ 结合。这些结果首次表明，慢性 HBV 感染患者 T 细胞激活的早期关键事件存在缺陷，这不仅有助于理解乙型肝炎免疫耐受，而且可能揭示新的潜在治疗靶点来控制感染。
