Germain Ronald N
Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Immunology. 2008 Jan;123(1):20-7. doi: 10.1111/j.1365-2567.2007.02779.x.
In the early 1970s a spate of papers by research groups around the world provided evidence for a negative regulatory role of thymus-derived lymphocytes (T cells). In 1971, Gershon and Kondo published a seminal paper in Immunology entitled 'Infectious Immunological Tolerance' indicating that such negative regulation could be a dominant effect that prevented otherwise 'helpful' T cells from mediating their function. Over the next decade, suppressor T cells, as these negative regulatory cells became known, were intensively investigated and a complex set of interacting cells and soluble factors were described as mediators in this process of immune regulation. In the early 1980s, however, biochemical and molecular experiments raised questions about the interpretation of the earlier studies, and within a few years, the term 'suppressor T cell' had all but disappeared from prominence and research on this phenomenon was held in poor esteem. While this was happening, new studies appeared suggesting that a subset of T cells played a critical role in preventing autoimmunity. These T cells, eventually dubbed 'regulatory T cells', have become a major focus of modern cellular immunological investigation, with a predominance that perhaps eclipses even that seen in the earlier period of suppressor T cell ascendancy. This brief review summarizes the rise and fall of 'suppressorology' and the possibility that Tregs are a modern rediscovery of suppressor T cells made convincing by more robust models for their study and better reagents for their identification and analysis.
20世纪70年代初,世界各地研究小组发表的一系列论文为胸腺来源的淋巴细胞(T细胞)的负调节作用提供了证据。1971年,格申(Gershon)和近藤(Kondo)在《免疫学》杂志上发表了一篇具有开创性的论文,题为《传染性免疫耐受》,表明这种负调节可能是一种主导效应,阻止了原本“有益”的T细胞发挥其功能。在接下来的十年里,这些负调节细胞被称为抑制性T细胞,受到了深入研究,一组复杂的相互作用细胞和可溶性因子被描述为免疫调节过程中的介质。然而,在20世纪80年代初,生化和分子实验对早期研究的解释提出了质疑,几年内,“抑制性T细胞”这个术语几乎不再突出,对这一现象的研究也不受重视。与此同时,新的研究表明,T细胞的一个亚群在预防自身免疫方面起着关键作用。这些T细胞最终被称为“调节性T细胞”,已成为现代细胞免疫学研究的主要焦点,其受关注程度甚至可能超过了早期抑制性T细胞占主导地位的时期。这篇简短的综述总结了“抑制性T细胞学说”的兴衰,以及调节性T细胞可能是抑制性T细胞的现代重新发现,这一观点因更强大的研究模型和更好的鉴定与分析试剂而更具说服力。