介绍： The Nobel-prize season always kicks off with the award for physiology or medicine, which highlights work in fields such as genetics, cell biology and evolution. This year’s award went to three researchers who tracked down how the immune system is regulated to stop it attacking the body of which it is part.每...

介绍： The Nobel-prize season always kicks off with the award for physiology or medicine, which highlights work in fields such as genetics, cell biology and evolution. This year’s award went to three researchers who tracked down how the immune system is regulated to stop it attacking the body of which it is part.每年诺贝尔奖总以生理学或医学奖率先揭幕，该奖项旨在表彰在遗传学、细胞生物学与进化等领域的重大科学突破。今年，评审委员会将这一荣誉授予三位科学家，他们揭示了免疫系统如何通过自我调节机制，避免攻击机体自身。
Mary Brunkow, Fred Ramsdell and Sakaguchi Shimon identified the cells responsible for what has come to be known as peripheral immune tolerance. These are specialised members of a class of immune-system cells called T-cells, and are now dubbed regulatory T-cells (Tregs). Their job is to stop other immune-system cells damaging the body’s organs. They are master controllers of various kinds of immune response, including allergy, autoimmunity and inflammation.玛丽·布伦科（Mary Brunkow）、弗雷德·拉姆斯德尔（Fred Ramsdell）与坂口志文（Sakaguchi Shimon）三人共同发现了负责“外周免疫耐受”（peripheral immune tolerance）的关键细胞。这些细胞属于T细胞家族中的一种特殊类型，被称为“调节性T细胞”（regulatory T cells，简称Tregs）。它们的任务是抑制其他免疫细胞对机体器官的误伤，是过敏、自身免疫及炎症等多种免疫反应的主控因子。
That may seem an obscure bit of biology to win such an esteemed prize. It is not. It is, rather, a piece of science fundamental to the development of medicines for cancer (the suppression of which needs a vigilant immune system) and autoimmunity (which needs it not to be too vigilant). The three winners will split the prize of SKr11m (about $1.2m).这一发现看似冷门，却并非如此。相反，它奠定了癌症与自身免疫疾病治疗的重要科学基础——前者需要激活免疫系统来清除肿瘤细胞，后者则需要让免疫反应保持克制，避免自我攻击。三位获奖者将平分1100万瑞典克朗（约合120万美元）的奖金。
The story starts in the 1980s, when Dr Sakaguchi, who is now at Osaka University but was then based in the Aichi Cancer Centre Research Institute in Nagoya, was inspired by experiments on mice, which found that removing the thymus (a small organ in the lymphatic system where T-cells mature, and which gives them their name) led to an increase in immune activity.故事要追溯到20世纪80年代。当时，现任大阪大学教授的坂口志文仍在名古屋爱知癌症中心研究所工作。他受到一项关于小鼠的实验启发——实验发现，切除胸腺（T细胞成熟的场所，也是其名称来源）的小鼠，其免疫活性反而增强。
This was unexpected. It had been assumed that removing the thymus would result in less immune activity. The new finding propelled him to search for the immunological peacekeeping force that must exist to keep the system in check—and thereby to a previously unknown class of immune cells which protect the body from autoimmune illnesses such as celiac disease, multiple sclerosis and type-1 diabetes.这一结果出乎意料。科学界原以为移除胸腺会削弱免疫功能。坂口由此推测，体内一定存在一种“免疫维和力量”，能防止免疫系统过度反应。最终，他确认了一类此前未知的免疫细胞，它们能保护机体免受乳糜泻、多发性硬化和1型糖尿病等自身免疫疾病的侵害。
Later, in 2001, Dr Brunkow and Dr Ramsdell, then working at Celltech Chiroscience, a British biotech firm, were investigating a strain of mice called “scurfy”, the males of which develop a severe and lethal autoimmune disorder. The restriction to males meant they knew the mutated gene causing the problem was on the X-chromosome (females are protected by having a second, unaffected X-chromosome), but even so, finding the exact gene concerned with the technology available 25 years ago was no mean feat.2001年，布伦科与拉姆斯德尔在英国生物技术公司Celltech Chiroscience工作时，研究了一种名为“scurfy”的小鼠品系。该品系的雄性小鼠会患上严重且致命的自身免疫疾病。由于发病仅限雄性，研究人员判断致病基因位于X染色体上（雌鼠因拥有第二条正常X染色体而免疫）。然而，在当时的技术条件下，定位这一基因并非易事。
When they did find it, they named it Foxp3. They then searched for equivalent genetic faults in humans, and found similar Foxp3 mutations in those with IPEX, a serious autoimmune condition. Two years later, Dr Sakaguchi connected the dots and proved that Foxp3 governs the development of Tregs.经过艰难探索，最终他们成功锁定该基因为Foxp3。随后，他们在患有严重自身免疫疾病IPEX综合征的人体样本中发现了相似的基因突变。两年后，坂口志文进一步证明，Foxp3基因正是调节性T细胞发育的关键控制因子。
Peripheral immune tolerance is now an area of great interest in drug development. Tregs maintain a fine balance between autoimmunity and immune suppression. Being able to tweak this to make Tregs more active, or less so, offers a rich seam of pharmaceutical potential.如今，“外周免疫耐受”已成为药物研发的前沿领域。Tregs在自身免疫与免疫抑制之间维持着精妙平衡。通过调节Tregs的活性——增强或削弱它们的功能——有望带来一系列新的治疗策略。
In cancer, for example, problems occur when Tregs are too protective—telling the immune system to reduce its activity when what is needed is for it to activate and respond strongly. One idea is to deplete the body of Tregs by developing antibody therapies that flag Tregs for destruction by other cells of the immune system.在癌症治疗中，问题在于Tregs过度抑制免疫系统，使机体无法有效攻击肿瘤。科学家正尝试利用抗体疗法“标记”Tregs，使免疫系统中的其他细胞将其清除，从而恢复免疫反应的活性。
In autoimmune conditions, by contrast, the problem is that Tregs are not protective enough. One approach is to extract and multiply them, and then re-introduce them into the body. PolTREG, a firm in Gdansk, Poland, is developing this type of cell therapy to treat type-1 diabetes. Abata Therapeutics, in Watertown, Massachusetts, is working on another to attack multiple sclerosis.而在自身免疫疾病中，问题则相反——Tregs抑制作用不足。一个思路是从患者体内提取并扩增Tregs，再回输以恢复免疫平衡。波兰格但斯克的生物公司PolTREG正开发此类细胞疗法，用于治疗Ⅰ型糖尿病；美国马萨诸塞州沃特敦的Abata Therapeutics公司则在研究类似疗法以应对多发性硬化症。
The upshot of the work of Drs Brunkow, Ramsdell and Sakaguchi may thus be new therapies for two quite different sorts of diseases. It is therefore an excellent example of physiology leading to medicine in the way the prize’s double name alludes to.布伦科、拉姆斯德尔与坂口志文的研究成果，或将催生针对两类截然不同疾病的新疗法。这正是“生理学与医学”奖名所体现的精髓——从对生命基本机制的理解，走向造福人类的医学实践。