Department of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, University Walk, Clifton, Bristol, United Kingdom.
Hum Immunol. 2010 Mar;71(3):225-34. doi: 10.1016/j.humimm.2009.12.003. Epub 2010 Jan 7.
Recent studies have expanded our understanding of the role of the anti-inflammatory cytokine interleukin (IL)-10, produced by multiple lineages of both human and murine T cells, in regulating the immune response. Here, we demonstrate that the small percentage of circulating CD4(+) T cells that secrete IL-10 can be isolated from human peripheral blood and, importantly, we have optimized a protocol to expand these cells in both antigen-specific and polyclonal manners. Expanded CD4(+)IL-10(+) T cells abrogate proliferation and T helper (Th) 1-like cytokine production in an antigen-specific manner, and to a lesser extent exhibit bystander suppressive capacity. CD4(+)IL-10(+) T cells are suppressive in a cell contact-dependent way, though they do not require secretion of IL-10 for their suppressive role in vitro. CD4(+)IL-10(+) T cells have an activated phenotype, with high expression of CD25, CD69, and cytotoxic T-lymphocyte antigen-4, and are largely FoxP3 negative. This novel method for the isolation and expansion of suppressive IL-10-secreting T cells has important implications both for further research and clinical therapeutic development.
最近的研究扩大了我们对抗炎细胞因子白细胞介素 (IL)-10 的作用的理解,这种细胞因子由人类和鼠类 T 细胞的多个谱系产生,可调节免疫反应。在这里,我们证明了能够从小鼠外周血中分离出分泌白细胞介素 (IL)-10 的少量循环 CD4(+)T 细胞,重要的是,我们已经优化了一种方案,以特异性和多克隆的方式扩增这些细胞。扩增的 CD4(+)IL-10(+)T 细胞以抗原特异性方式消除增殖和辅助性 T 细胞(Th)1 样细胞因子的产生,并且在较小程度上表现出旁观者抑制能力。CD4(+)IL-10(+)T 细胞以细胞接触依赖性方式发挥抑制作用,但它们在体外发挥抑制作用时不需要分泌白细胞介素-10。CD4(+)IL-10(+)T 细胞具有激活的表型,高表达 CD25、CD69 和细胞毒性 T 淋巴细胞抗原-4,并且很大程度上是 FoxP3 阴性的。这种用于分离和扩增抑制性白细胞介素-10 分泌 T 细胞的新方法对于进一步的研究和临床治疗的发展具有重要意义。