Henson Sian M, Snelgrove Robert, Hussell Tracy, Wells Dominic J, Aspinall Richard
Department of Immunology, Imperial College, Chelsea and Westminster Hospital, London, United Kingdom.
J Immunol. 2005 Sep 15;175(6):4112-8. doi: 10.4049/jimmunol.175.6.4112.
The role of IL-7 during thymopoiesis has led to it being the focus of a number of therapeutic interventions. However, its small size and pleiotropic nature present problems for thymus-directed therapies. We have created a fusion molecule between the extracellular N-terminal domain of CCR9 and IL-7, which has the potential to overcome these difficulties. This novel fusion protein retains the thymopoietic activity of IL-7 and the ligand-binding ability of CCR9. As a thymopoietic agent, compared with IL-7, it shows an enhanced retention in the thymus, increased de novo T cell production, and increased thymic output. Old mice receiving the fusion protein show improved CD8 T cell responses and reduced viral load after infection with influenza virus compared with those receiving IL-7. This chimeric molecule offers a novel therapeutic strategy that may result in the production of an effective immunorestorative agent.
白细胞介素-7（IL-7）在胸腺生成过程中的作用使其成为多种治疗干预措施的焦点。然而，其体积小和多效性的特点给针对胸腺的治疗带来了问题。我们构建了趋化因子受体9（CCR9）细胞外N端结构域与IL-7之间的融合分子，它有可能克服这些困难。这种新型融合蛋白保留了IL-7的胸腺生成活性和CCR9的配体结合能力。作为一种胸腺生成剂，与IL-7相比，它在胸腺中的保留时间延长，新生T细胞产生增加，胸腺输出增加。与接受IL-7的老年小鼠相比，接受融合蛋白的老年小鼠在感染流感病毒后表现出改善的CD8 T细胞反应和降低的病毒载量。这种嵌合分子提供了一种新的治疗策略，可能会产生一种有效的免疫恢复剂。
