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Response to self antigen imprints regulatory memory in tissues

机译：对自身抗原的反应会在组织中留下调节性记忆

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摘要

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 duration. In fact, these diseases often spontaneously resolve, despite persistent tissue autoantigen expression. 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 exposure. 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 (T_(reg) 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 T_(reg) cells are maintained in the target tissue and are primed to attenuate subsequent autoimmune reactions when antigen is re-expressed. Thus, T_(reg) cells function to confer 'regulatory memory' to the target tissue. These findings provide a framework for understanding how T_(reg) cells respond when exposed to self antigen in peripheral tissues and offer mechanistic insight into how tissues regulate autoimmunity.
机译：通过针对组织特异性抗原的致病性T细胞应答与组织抑制这些应答的能力之间的微妙平衡，可以实现组织中的免疫稳态。目前尚不清楚组织和免疫系统进行通信以建立和维持免疫稳态的机制。临床证据表明，长期或反复暴露于组织内的自身抗原会导致病理性自身免疫反应减弱，可能是减轻炎症损伤和保持功能的一种手段。许多人类器官特异性自身免疫性疾病的特征是该疾病的最初表现是最严重的，随后爆发的严重性和持续时间较小。实际上，尽管持续表达组织自身抗原，但这些疾病通常会自发消退。在抗原特异性免疫疗法的实践中，过敏原或自身抗原被反复注射到皮肤中，在每次连续暴露后发炎反应减少。尽管这些发现表明组织在对抗原重复反应后具有减弱自身免疫反应的能力，但其发生机理尚不清楚。在这里，我们显示出在外周组织中表达自身抗原后，源自胸腺的调节性T细胞（T_（reg）细胞）被激活，增殖并分化成更有效的抑制剂，从而介导小鼠器官特异性自身免疫的消退。炎症反应消退后，活化的T_（reg）细胞将保留在靶组织中，并在抗原重新表达时被灌注以减弱随后的自身免疫反应。因此，T_（reg）细胞的功能是赋予靶组织“调节记忆”。这些发现为了解T_（reg）细胞暴露于周围组织自身抗原中时如何反应提供了框架，并为了解组织如何调节自身免疫性提供了机制性见解。

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  • 来源
    《Nature》 |2011年第7378期|p.538-542|共5页
  • 作者

    Michael D. Rosenblum; Iris K. Gratz; Jonathan S. Paw; Karen Lee; Ann Marshak-Rothstein; Abul K. Abbas;

  • 作者单位

    Department of Dermatology, University of California San Francisco, San Francisco, Caiifornia 94115, USA.;

    Department of Pathology, University of California San Francisco, San Francisco, California 94143, USA.;

    Department of Dermatology, University of California San Francisco, San Francisco, Caiifornia 94115, USA. ,Department of Pathology, University of California San Francisco, San Francisco, California 94143, USA.;

    Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA.;

    Department of Medicine, Rheumatology Division, University of Massachusetts, Worcester,Massachusetts 01655, USA.;

    Department of Pathology, University of California San Francisco, San Francisco, California 94143, USA.;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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