Thomas Tedder及其同事发现,依赖于IL-21和CD40的、与T-细胞的同源相互作用是生成能够产生CD5+调控性B-细胞的IL-10的关键驱动因素。在试管中转移扩大的调控性B细胞,被发现在具有多发性硬化的实验性自体免疫脑脊髓炎小鼠模型中能够抑制疾病症状。这为目前还缺乏有效疗法的严重自体免疫疾病的治疗提供了新策略。

-2012年11月8日《自然》

#800000;”>中文翻译


【题目】调节性B细胞通过IL-21依赖的同源相互作用控制T细胞自身免疫

【译文】B细胞通过产生抗原特异性抗体来调控免疫反应。然而,一些特异性B细胞亚型也可以负调控T细胞免疫反应,因此命名为调节性B细胞。目前已经证实人和鼠调节性B细胞(B10细胞)具有表达抑制性细胞因子白介素10(IL-10)的能力。尽管比较少见,B10细胞是小鼠中抗原特异性炎症反应和T细胞依赖的自身免疫病的有效负性调控因子。体内如何控制B10细胞产生IL-10及如何控制抗原特异性免疫反应且不会诱导全身免疫抑制作用,相关的机制目前尚不清楚。利用多发性硬化症的小鼠模型,本研究表明B10细胞成熟形成的在体内抑制自身免疫病的、可分泌IL-10的功能性效应细胞需要与T细胞之间、IL-21和CD40依赖的同种相互作用。此外,体外提供CD40和IL-21受体信号可驱动B10细胞发育和400万倍的扩展,并形成可产生IL-10的B10细胞效应细胞,当转移至自身免疫病小鼠体内时,这种细胞可以显著抑制疾病症状。自体B10细胞的体外扩展和再输注可能为当前疗法耐受的严重自身免疫病提供新的有效的体内疗法。

英文原稿


[Title]: Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions

[Authors]:Ayumi Yoshizaki,1, 3 Tomomitsu Miyagaki,1, 3 David J. DiLillo,1 Takashi Matsushita,1 Mayuka Horikawa,1 Evgueni I. Kountikov,1 Rosanne Spolski,2 Jonathan C. Poe,1 Warren J. Leonard2 & Thomas F. Tedder1, 3

[Abstract]:B cells regulate immune responses by producing antigen-specific antibodies. However, specific B-cell subsets can also negatively regulate T-cell immune responses, and have been termed regulatory B cells. Human and mouse regulatory B cells (B10 cells) with the ability to express the inhibitory cytokine interleukin-10 (IL-10) have been identified. Although rare, B10 cells are potent negative regulators of antigen-specific inflammation and T-cell-dependent autoimmune diseases in mice. How B10-cell IL-10 production and regulation of antigen-specific immune responses are controlled in vivo without inducing systemic immunosuppression is unknown. Using a mouse model for multiple sclerosis, here we show that B10-cell maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T cells. Moreover, the ex vivo provision of CD40 and IL-21 receptor signals can drive B10-cell development and expansion by four-million-fold, and generate B10 effector cells producing IL-10 that markedly inhibit disease symptoms when transferred into mice with established autoimmune disease. The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.

原文地址

http://www.nature.com/nature/journal/v491/n7423/full/nature11501.html

 

 

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