生物谷報(bào)道：最近，一項(xiàng)新的研究顯示了機(jī)體對(duì)抗免疫系統(tǒng)相關(guān)疾病，包括腫瘤和自身免疫疾病如I型糖尿病和關(guān)節(jié)炎等疾病的一種不同尋常的方式 ,。該研究由維康基金會(huì)（Wellcome Trust）投資，結(jié)果發(fā)表在《自然》雜志的網(wǎng)絡(luò)版,。
過(guò)去,，科學(xué)家發(fā)現(xiàn)了兩類T細(xì)胞，都產(chǎn)生于胸腺：攻擊感染細(xì)胞的“效應(yīng)T細(xì)胞”和抑制免疫系統(tǒng)以保護(hù)機(jī)體不受感染時(shí)炎癥損傷的“調(diào)解T細(xì)胞”,。如果是接受了移植的個(gè)體,，輸注調(diào)解T細(xì)胞可能會(huì)有助于抑制排斥反應(yīng)。
現(xiàn)在,，一組研究人員已經(jīng)發(fā)現(xiàn)了決定來(lái)自于胸腺的成熟T細(xì)胞究竟是效應(yīng)細(xì)胞還是調(diào)解細(xì)胞的一個(gè)新機(jī)制,。該研究提示了對(duì)免疫系統(tǒng)相關(guān)疾病的新的治療方法，即有目的的影響所產(chǎn)生的T細(xì)胞類型,，從而解決許多由T細(xì)胞類型的不同所影響的疾病,。
原文出處：
T for Two: Scientists Show How Immune System Chooses Best Way to Fight Infection
11/14/06 -- A new study has suggested a novel way of combating diseases related to the immune system, including cancer and autoimmune diseases such as type I diabetes and arthritis. The study, funded by the Wellcome Trust, appears online in the journal Nature.
T cells are produced by the body to fight infection. Scientists previously identified two types of T cell, both produced in the thymus: "effector T cells", which attack infected cells, and "regulatory T cells", which suppress the immune system, protecting the body from inflammatory damage during infection. Regulatory T cells, if given to individuals receiving transplants, may help suppress the rejection response.
Now, a team of researchers has discovered a novel mechanism determining whether a maturing T cell is likely to emerge from the thymus as an effector cell or a regulatory cell. The research suggests that new treatments could be developed to deliberately affect the type of T cells produced, allowing scientists to tackle a number of diseases which are influenced by these different types of T cells.
"Our team has shown that a process known as 'trans-conditioning', which we knew to be involved in T cell development, actually has a profound influence on whether a T cell becomes an effector or a regulatory cell," explains Professor Adrian Hayday of King's College London. "This may be clinically significant; if we can find a way to influence this process, it may be possible to make the body produce effector T cells in a cancer patient or regulatory T cells in someone suffering from autoimmune disease, both of which are caused by the immune system malfunctioning."
Professor Hayday and his team believe that the findings may also answer one of medical research's mysteries: why autoimmune diseases in women commonly go into remission in pregnancy.
"We believe that trans-conditioning is less active during pregnancy," says Professor Hayday. "This means that most T cells emerging at that time will be regulatory. Regulatory T cells prevent an over-active immune system from causing inflammatory damage to the body. This may be one of the key steps in preventing the mother from rejecting the foetus growing inside her."
Source: Wellcome Trust
背景知識(shí)：
1、前言：調(diào)節(jié)性T 細(xì)胞(regulatory T cell,，Tr)是一群通過(guò)細(xì)胞間接觸和產(chǎn)生抑制性細(xì)胞因子發(fā)揮免疫抑制作用,，以調(diào)節(jié)自身T 細(xì)胞為主要功能的T 細(xì)胞亞群。在腫瘤,、自身免疫疾病和移植等免疫相關(guān)患者中,，許多由自身T 細(xì)胞識(shí)別的自體或異體抗原是誘發(fā)機(jī)體免疫反應(yīng)的導(dǎo)火索。近年來(lái)隨著研究的進(jìn)一步深入，發(fā)現(xiàn)在眾多具有調(diào)節(jié)性的T細(xì)胞亞群中,，CD4+CD25+Tr 是一個(gè)極其重要亞群,。
2、背景：1990年,，Hall等報(bào)道在接受環(huán)孢素A治療的心臟移植大鼠體內(nèi),，一種表達(dá)OX39(CD25， 白細(xì)胞介素—２受體α鏈)的CD4+ T細(xì)胞亞群可介導(dǎo)移植物特異的低反應(yīng)性和免疫抑制作用,。1995 年,，Sakaguchi等發(fā)現(xiàn)將除去CD4+CD25+組分的T細(xì)胞轉(zhuǎn)移至裸鼠體內(nèi)可以導(dǎo)致炎癥性腸病、自身免疫性胃炎的多種自身免疫疾病的發(fā)生,， 同時(shí)輸入CD4+CD25+ T 細(xì)胞可以抑制自身免疫疾病的,。這種CD4+CD25+ T 細(xì)胞不同于活化的表達(dá)CD25 的CD4+CD25- T細(xì)胞，在隨后的一系列研究中被證實(shí)是一種在體內(nèi)自然產(chǎn)生的抑制性T細(xì)胞,，具有低反應(yīng)性和免疫抑制作用,，稱之為調(diào)節(jié)性T細(xì)胞（Treg）．這種調(diào)節(jié)性T細(xì)胞不但對(duì)異體抗原具有低反應(yīng)性，而且還可以抑制自身反應(yīng)性T細(xì)胞的功能,。Treg盡管最初是在大鼠和小鼠體內(nèi)被發(fā)現(xiàn),，但隨后在人中和其他靈長(zhǎng)類動(dòng)物體內(nèi)也發(fā)現(xiàn)了具有同樣表型和功能特性的調(diào)節(jié)性T細(xì)胞。這種T細(xì)胞可以抑制各種各樣的自身免疫性疾病,，使之成為誘導(dǎo)免疫耐受的一個(gè)重要因素,。從此大量的研究集中到了對(duì)Treg作用機(jī)制以及其臨床應(yīng)用價(jià)值的探索。
3,、概述：調(diào)節(jié)性T 細(xì)胞（Regulatory T cell, Treg）是一種天然產(chǎn)生的在體內(nèi)外發(fā)揮免疫調(diào)節(jié)作用,、導(dǎo)致免疫耐受的重要CD4+T 細(xì)胞亞型。由于其表面表達(dá)CD25（IL-2 受體α鏈）,，一直以來(lái)以CD4+CD25+ T 細(xì)胞作為Treg 的代名詞,。這種T 細(xì)胞不僅對(duì)自身或異體抗原具有低反應(yīng)性，而且還可以通過(guò)細(xì)胞接觸的方式抑制效應(yīng)T 細(xì)胞的活化,、增殖及效應(yīng)功能,，從而發(fā)揮其免疫抑制作用。同時(shí),，活化的Treg 還可分泌多種細(xì)胞因子如IL-10,、IL-4、TGF-β等參與其抑制作用,。1990年,，Hall等報(bào)道在接受環(huán)孢素A治療的心臟移植大鼠體內(nèi)，一種表達(dá)OX39(CD25)的CD4+ T細(xì)胞亞群可介導(dǎo)移植物特異的低反應(yīng)性和免疫抑制作用,。1995 年,，Sakaguchi等發(fā)現(xiàn)將除去CD4+CD25+組分的T細(xì)胞轉(zhuǎn)移至裸鼠體內(nèi)可以導(dǎo)致炎癥性腸病,、自身免疫性胃炎的多種自身免疫疾病的發(fā)生，同時(shí)輸入CD4+CD25+ T 細(xì)胞可以抑制自身免疫疾病,。盡管Treg最初是在大鼠和小鼠體內(nèi)被發(fā)現(xiàn),，但隨后在人中和其他靈長(zhǎng)類動(dòng)物體內(nèi)也發(fā)現(xiàn)了具有同樣表型和功能特性的調(diào)節(jié)性T細(xì)胞
4、來(lái)源：在體內(nèi)自然產(chǎn)生的調(diào)節(jié)性T細(xì)胞有兩種來(lái)源：胸腺來(lái)源和外周來(lái)源,。
5,、作用機(jī)制：調(diào)節(jié)性T細(xì)胞在自身免疫耐受的維持和對(duì)非自身抗原免疫反應(yīng)的負(fù)性調(diào)節(jié)中發(fā)揮著重要作用。在過(guò)去的幾年,，盡管對(duì)調(diào)節(jié)性T細(xì)胞的作用機(jī)制作了大量的研究,，但仍不明確它是如何發(fā)揮其免疫抑制作用的。盡管體內(nèi)和體外的研究顯示其可能作用機(jī)制有很大的爭(zhēng)論,，但細(xì)胞接觸依賴和細(xì)胞因子依賴可能是調(diào)節(jié)性T細(xì)胞作用機(jī)制的兩種相互協(xié)調(diào)的方式
6,、應(yīng)用：調(diào)節(jié)性T細(xì)胞的免疫抑制作用在臨床應(yīng)用的研究中得到廣泛的重視，可分為兩大方向：一方面研究如何誘導(dǎo)和增強(qiáng)調(diào)節(jié)性T細(xì)胞的作用從而抑制自身免疫疾病的發(fā)生,、減輕感染時(shí)的破壞性炎癥反應(yīng),、減少器官移植后的移植排斥誘導(dǎo)免疫耐受；另一方面研究如何抑制調(diào)節(jié)性T細(xì)胞的作用從而增強(qiáng)對(duì)病原微生物和腫瘤的抵抗能力,。在動(dòng)物和人體實(shí)驗(yàn)中發(fā)現(xiàn)調(diào)節(jié)性T細(xì)胞可抑制多種自身免疫疾病,在細(xì)菌,、真菌,、病毒以及寄生蟲等引起的感染中調(diào)節(jié)性T細(xì)胞可以抑制過(guò)強(qiáng)的炎癥反應(yīng),，使之趨于慢性化，從而減輕癥狀改善病情,。在接受各種同種異體移植的患者中,，調(diào)節(jié)性T細(xì)胞對(duì)于防止慢性免疫排斥，延長(zhǎng)移植物存活時(shí)間有重要意義,。
