生物谷綜合：德國海德堡癌癥研究中心的科學(xué)家發(fā)現(xiàn)了多發(fā)性硬化新的機(jī)理,，即患者體內(nèi)無法形成足夠的免疫細(xì)胞,，結(jié)果導(dǎo)致神經(jīng)系統(tǒng)的破壞。
海德堡癌癥研究中心的科學(xué)家發(fā)現(xiàn),，多發(fā)性硬化患者的胸腺內(nèi)缺乏重要的免疫細(xì)胞,，即所謂起調(diào)節(jié)作用的T細(xì)胞，這就無法阻止患者的神經(jīng)系統(tǒng)的破壞,，這一研究結(jié)果刊登在最新一期《免疫學(xué)雜志》上,。
這項(xiàng)研究結(jié)果對治療多發(fā)性硬化癥具有重要意義，早在2003年海德堡癌癥研究中心的科學(xué)家就發(fā)現(xiàn),，胸腺對于多發(fā)性硬化的產(chǎn)生起重要的作用,，2年前專家又指出，起調(diào)節(jié)作用的T細(xì)胞對多發(fā)性硬化患者具有特殊的功能,，而最新的研究成果是將兩者的研究結(jié)果綜合到一起,。
新的研究結(jié)果可以解釋為什么特定的藥物對治療多發(fā)性硬化癥起作用，為什么女性多發(fā)性硬化癥患者在孕期通常感覺特別好,，這都是因?yàn)楹蔂柮珊吞囟ǖ乃幬锍煞謱π叵俟δ芩a(chǎn)生的影響,，形成了新的抵御細(xì)胞?；谛碌恼J(rèn)識,，可以采用新的方法來治療多發(fā)性硬化癥,。該研究項(xiàng)目的實(shí)驗(yàn)室主任于爾根·哈斯稱，“可以提取患者體內(nèi)具有完全活性的T細(xì)胞，然后在細(xì)胞核內(nèi)進(jìn)行繁殖,，再注射回患者體內(nèi),，這樣可能對病癥起很好的正面作用,。”
僅德國就有8萬人患多發(fā)性硬化癥，這種病常常發(fā)生在成年人早期,，女性得病的比率又高于男性。得了多發(fā)性硬化會(huì)不斷破壞人體內(nèi)健康的神經(jīng)組織,，導(dǎo)致發(fā)癢,、知覺受損、肢體麻痹,、萎靡不振,、以及視力障礙，目前還沒有藥物能完全治愈這種疾病,。(科技日報(bào))
原始出處:
The Journal of Immunology, 2007, 179: 1322-1330.
Prevalence of Newly Generated Naive Regulatory T Cells (Treg) Is Critical for Treg Suppressive Function and Determines Treg Dysfunction in Multiple Sclerosis1
Jürgen Haas*, Benedikt Fritzsching*,, Petra Trübswetter*, Mirjam Korporal*, Linda Milkova*, Brigitte Fritz*, Diana Vobis, Peter H. Krammer, Elisabeth Suri-Payer and Brigitte Wildemann2,*
* Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany; and Division of Immunogenetics/Tumorimmunology Program, Deutsches Krebsforschungszentrum, Heidelberg, Germany
The suppressive function of regulatory T cells (Treg) is impaired in multiple sclerosis (MS) patients. The mechanism underlying the Treg functional defect is unknown. Treg mature in the thymus and the majority of cells circulating in the periphery rapidly adopt a memory phenotype. Because our own previous findings suggest that the thymic output of T cells is impaired in MS, we hypothesized that an altered Treg generation may contribute to the suppressive deficiency. We therefore determined the role of Treg that enter the circulation as recent thymic emigrants (RTE) and, unlike their CD45RO+ memory counterparts, express CD31 as typical surface marker. We show that the numbers of CD31+-coexpressing CD4+CD25+CD45RA+CD45RO–FOXP3+ Treg (RTE-Treg) within peripheral blood decline with age and are significantly reduced in MS patients. The reduced de novo generation of RTE-Treg is compensated by higher proportions of memory Treg, resulting in a stable cell count of the total Treg population. Depletion of CD31+ cells from Treg diminishes the suppressive capacity of donor but not patient Treg and neutralizes the difference in inhibitory potencies between the two groups. Overall, there was a clear correlation between Treg-mediated suppression and the prevalence of RTE-Treg, indicating that CD31-expressing naive Treg contribute to the functional properties of the entire Treg population. Furthermore, patient-derived Treg, but not healthy Treg, exhibit a contracted TCR V repertoire. These observations suggest that a shift in the homeostatic composition of Treg subsets related to a reduced thymic-dependent de novo generation of RTE-Treg with a compensatory expansion of memory Treg may contribute to the Treg defect associated with MS.
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1 This work was supported by the Gemeinnützige Hertie-Stiftung (1.01.1/04/003), Deutsche Forschungsgemeinschaft (Sonderforschungsbereich (SFB) 405, 5H and SFB 571, B7), the Young Investigator Award from the Faculty of Medicine, University of Heidelberg (to B.F.), and Serono Deutschland GmbH.
2 Address correspondence and reprint requests to Dr. Brigitte Wildemann, Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, INF 350, Heidelberg, Germany. E-mail address: [email protected]
3 Abbreviations used in this paper: Treg, regulatory T cell; CS, complexity score; GA, glatiramer acetate; HC, healthy control; MS, multiple sclerosis; RRMS, relapsing remitting MS; RTE, recent thymic emigrant; Teff, effector T cell; TREC, TCR excision circle.
