The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Cell. 2011 Feb 18;144(4):601-13. doi: 10.1016/j.cell.2011.01.011. Epub 2011 Feb 3.
Understanding the factors that impede immune responses to persistent viruses is essential in designing therapies for HIV infection. Mice infected with LCMV clone-13 have persistent high-level viremia and a dysfunctional immune response. Interleukin-7, a cytokine that is critical for immune development and homeostasis, was used here to promote immunity toward clone-13, enabling elucidation of the inhibitory pathways underlying impaired antiviral immune response. Mechanistically, IL-7 downregulated a critical repressor of cytokine signaling, Socs3, resulting in amplified cytokine production, increased T cell effector function and numbers, and viral clearance. IL-7 enhanced thymic output to expand the naive T cell pool, including T cells that were not LCMV specific. Additionally, IL-7 promoted production of cytoprotective IL-22 that abrogated liver pathology. The IL-7-mediated effects were dependent on endogenous IL-6. These attributes of IL-7 have profound implications for its use as a therapeutic in the treatment of chronic viral diseases.
了解阻碍持续性病毒免疫反应的因素对于设计 HIV 感染的治疗方法至关重要。感染 LCMV 克隆-13 的小鼠会持续出现高水平的病毒血症和功能失调的免疫反应。细胞因子白细胞介素 7（IL-7）对于免疫发育和稳态至关重要，它被用于促进对克隆-13 的免疫反应，从而阐明了抑制抗病毒免疫反应的抑制途径。从机制上讲，IL-7 下调了细胞因子信号的关键抑制剂 Socs3，导致细胞因子产生增加、T 细胞效应功能和数量增加以及病毒清除。IL-7 增强了胸腺输出，扩大了幼稚 T 细胞池，包括非 LCMV 特异性的 T 细胞。此外，IL-7 促进了具有保护作用的细胞因子白细胞介素 22（IL-22）的产生，从而减轻了肝脏病变。IL-7 的这种介导作用依赖于内源性的白细胞介素 6（IL-6）。IL-7 的这些特性对其作为治疗慢性病毒疾病的治疗方法具有深远的意义。
