Nature：免疫保护性记忆细胞

　　

生物通报道  在多数情况下机体能够在免疫调控机制的精密控制下,通过适度的免疫应答防止病原微生物的入侵、监视并清除机体内恶变的细胞同时保持内环境的稳定,但是,一旦这样的调控机制出现异常,将会导致免疫病理反应从而对机体造成伤害,如自身免疫性疾病等。

长期以来,对于增强免疫应答效应的免疫调控机制即正相免疫调控机制的研究较多且较为深入,而对于免疫负相调控的机制则认识不足。因此近年来免疫学领域有关免疫负相调控机制的研究非常热门,其中最大的热点就是具有负调节机体免疫反应功能的调节T细胞(Regulatory T cell，Treg)。

近日来自加州大学旧金山分校（UCSF）的研究人员利用一种自身免疫性疾病的小鼠模型发现Treg细胞充当了“保护性记忆细胞”的角色，帮助提醒免疫系统避免攻击自身的分子、细胞和器官。这一研究发现有可能帮助研究人员找到对抗一系列自身免疫性疾病以及防止移植免疫排斥的新策略。相关研究论文在线发表11月27日的《自然》（Nature）杂志上。

在自身免疫性疾病中，淋巴细胞错误地识别和攻击“自身”的蛋白。大多数情况下都涉及到了Treg细胞的异常反应。近年来免疫学家们逐步认识到Treg细胞不仅在感染恢复期参与抑制了免疫反应，并且防止自身免疫应答中亦发挥着重要的作用。例如，他们发现机体的皮肤可通过活化少量的Treg细胞保护免受自身免疫攻击。

在这篇文章中，加州大学旧金山分校的研究人员在小鼠试验中证实，胸腺来源的Treg在接触到外周组织中的自身抗原后被激活，继而增殖，分化形成了更有效的自身免疫抑制细胞。在发生免疫反应后，这些活化的Treg细胞可保留在靶组织中，当再次遭遇相同的抗原时可帮助减轻随后的自身免疫反应。这表明Treg在这些靶组织中起着重要的免疫记忆调控功能。

目前科学家们已在一些旨在防止器官移植免疫排斥的治疗中针对Treg细胞展开了研究，新研究发现了具有长期记忆功能的Treg细胞群，从而为更深入地揭示机体自身免疫疾病和移植免疫排斥的分子机理，以及开发出有效的治疗策略指明了新的方向。

（生物通：何嫱）

生物通推荐原文摘要：

Response to self antigen imprints regulatory memory in tissues

Immune homeostasis in tissues is achieved through a delicate balance between pathogenic T-cell responses directed at tissue-specific antigens and the ability of the tissue to inhibit these responses. The mechanisms by which tissues and the immune system communicate to establish and maintain immune homeostasis are currently unknown. Clinical evidence suggests that chronic or repeated exposure to self antigen within tissues leads to an attenuation of pathological autoimmune responses, possibly as a means to mitigate inflammatory damage and preserve function. Many human organ-specific autoimmune diseases are characterized by the initial presentation of the disease being the most severe, with subsequent flares being of lesser severity and duration1. In fact, these diseases often spontaneously resolve, despite persistent tissue autoantigen expression2. In the practice of antigen-specific immunotherapy, allergens or self antigens are repeatedly injected in the skin, with a diminution of the inflammatory response occurring after each successive exposure3. Although these findings indicate that tissues acquire the ability to attenuate autoimmune reactions upon repeated responses to antigens, the mechanism by which this occurs is unknown. Here we show that upon expression of self antigen in a peripheral tissue, thymus-derived regulatory T cells (Treg cells) become activated, proliferate and differentiate into more potent suppressors, which mediate resolution of organ-specific autoimmunity in mice. After resolution of the inflammatory response, activated Treg cells are maintained in the target tissue and are primed to attenuate subsequent autoimmune reactions when antigen is re-expressed. Thus, Treg cells function to confer ‘regulatory memory’ to the target tissue. These findings provide a framework for understanding how Treg cells respond when exposed to self antigen in peripheral tissues and offer mechanistic insight into how tissues regulate autoimmunity.