日本研究人员发现，两种蛋白质相互作用可调节抑制性Ｔ细胞的活动，从而从分子水平上揭示了抑制性Ｔ细胞抑制免疫应答的机制。
根据京都大学日前发布的新闻公报，来自京都大学再生医学研究所、日本科学技术振兴机构和国立癌症中心研究所的研究人员发现，两种与抑制性Ｔ细胞有关的特殊蛋白质一旦结合，可抑制免疫反应，它们分别是只有抑制性Ｔ细胞能够合成的蛋白质“Ｆｏｘｐ３”，以及对抑制性Ｔ细胞发挥功能起关键作用的蛋白质——“ＡＭＬ１”。进一步分析显示，这两种蛋白质一旦结合，就会抑制合成白介素２的基因表达，而白介素２是放大免疫应答的主要信息传递物质。
抑制性Ｔ细胞是一种特殊的淋巴细胞，它不仅能抑制自体免疫疾病，也会抑制针对肿瘤等的有益免疫反应。新闻公报说，这一研究成果为通过干扰“Ｆｏｘｐ３”和“ＡＭＬ１”的相互作用，自由操控抑制性Ｔ细胞提供了可能性。
研究人员指出，这一发现不仅有助于探究自体免疫疾病和过敏症的发病机理，也为开发治疗免疫疾病、抑制脏器移植时的排异反应、激活针对癌症的免疫反应等方面的新药物打下了基础。
有关研究论文发表在最新出版的英国《自然》杂志上。
部分英文原文：
Nature advance online publication 21 March 2007 | doi:10.1038/nature05673; Received 12 December 2006; Accepted 9 February 2007; Published online 21 March 2007
Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1
Masahiro Ono1,2,6, Hiroko Yaguchi3,6, Naganari Ohkura3,6, Issay Kitabayashi4, Yuko Nagamura3, Takashi Nomura1, Yoshiki Miyachi2, Toshihiko Tsukada3 and Shimon Sakaguchi1,5
Department of Experimental Pathology, Institute for Frontier Medical Sciences, and
Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
Tumor Endocrinology Project, and,
Molecular Oncology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan
Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi 332-0012, Japan
These authors contributed equally to this work.
Correspondence to: Shimon Sakaguchi1,5 Correspondence and requests for materials should be addressed to S.S. (Email: shimon@frontier.kyoto-u.ac.jp).
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Naturally arising CD25+CD4+ regulatory T cells (TR cells) are engaged in the maintenance of immunological self-tolerance and immune homeostasis by suppressing aberrant or excessive immune responses, such as autoimmune disease and allergy1, 2, 3. TR cells specifically express the transcription factor Foxp3, a key regulator of TR-cell development and function. Ectopic expression of Foxp3 in conventional T cells is indeed sufficient to confer suppressive activity, repress the production of cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-), and upregulate TR-cell-associated molecules such as CD25, cytotoxic T-lymphocyte-associated antigen-4, and glucocorticoid-induced TNF-receptor-family-related protein4, 5, 6, 7. However, the method by which Foxp3 controls these molecular events has yet to be explained. Here we show that the transcription factor AML1 (acute myeloid leukaemia 1)/Runx1 (Runt-related transcription factor 1), which is crucially required for normal haematopoiesis including thymic T-cell development8, 9, 10, 11, activates IL-2 and IFN- gene expression in conventional CD4+ T cells through binding to their respective promoters. In natural TR cells, Foxp3 interacts physically with AML1. Several lines of evidence support a model in which the interaction suppresses IL-2 and IFN- production, upregulates TR-cell-associated molecules, and exerts suppressive activity. This transcriptional control of TR-cell function by an interaction between Foxp3 and AML1 can be exploited to control physiological and pathological T-cell-mediated immune responses.
