生物谷综合：德国海德堡癌症研究中心的科学家发现了多发性硬化新的机理，即患者体内无法形成足够的免疫细胞，结果导致神经系统的破坏。
海德堡癌症研究中心的科学家发现，多发性硬化患者的胸腺内缺乏重要的免疫细胞，即所谓起调节作用的T细胞，这就无法阻止患者的神经系统的破坏，这一研究结果刊登在最新一期《免疫学杂志》上。
这项研究结果对治疗多发性硬化症具有重要意义，早在2003年海德堡癌症研究中心的科学家就发现，胸腺对于多发性硬化的产生起重要的作用，2年前专家又指出，起调节作用的T细胞对多发性硬化患者具有特殊的功能，而最新的研究成果是将两者的研究结果综合到一起。
新的研究结果可以解释为什么特定的药物对治疗多发性硬化症起作用，为什么女性多发性硬化症患者在孕期通常感觉特别好，这都是因为荷尔蒙和特定的药物成分对胸腺功能所产生的影响，形成了新的抵御细胞。基于新的认识，可以采用新的方法来治疗多发性硬化症。该研究项目的实验室主任于尔根·哈斯称，“可以提取患者体内具有完全活性的T细胞，然后在细胞核内进行繁殖，再注射回患者体内，这样可能对病症起很好的正面作用。”
仅德国就有8万人患多发性硬化症，这种病常常发生在成年人早期，女性得病的比率又高于男性。得了多发性硬化会不断破坏人体内健康的神经组织，导致发痒、知觉受损、肢体麻痹、萎靡不振、以及视力障碍，目前还没有药物能完全治愈这种疾病。(科技日报)
原始出处:
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: brigitte_wildemann@med.uni-heidelberg.de
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.
