Characterization of lymphocytes that suppress EAE

实验性自身免疫性脑脊髓炎是一种炎性脱髓鞘 中枢神经系统（CNS）疾病作为多种疾病的模型进行研究 硬化症携带单克隆髓鞘碱性蛋白（MBP）特异性 ab T细胞区室自发地发展EAE。EAE可以预防， 这些小鼠通过给予少量多克隆CD 4 + T细胞 （调节性T细胞或T-reg）属于CD 4 + CD 25+或CD 4 + CD 25+。 CD 4 + CD 25- T细胞亚群。T-reg给药的生物学影响 是大的，因此，其临床应用的潜力也是如此，但许多 控制自发性EAE的T-reg细胞的重要特性仍然很差 明白此应用程序侧重于涉及的关键事件， MBP特异性T细胞受体对自发性EAE免疫调节作用 转基因小鼠在目标1中，我们将评估细胞因子，细胞因子 受体和共刺激分子IL-2，CD 25，IL-10，TGF-β和CD 28 T-reg的产生、存活和功能。更好地了解T-reg 对这些细胞因子和共刺激信号的依赖可能会增强 免疫调节性T细胞的体内操作的潜力。在目标2中，我们 研究调节性T细胞的MHC限制。MHC的特性 限制T-reg细胞可能有助于设计纯化这些细胞的策略 从总的CD 4 + T细胞区室中分离。

Experimental autoimmune encephalomyelitis is an inflammatory demyelinating disease of the central nervous system (CNS) studied as a model of multiple sclerosis. Mice which harbor a monoclonal myelin basic protein (MBP)-specific ab T cell compartment develop EAE spontaneously. EAE can be prevented in these mice by the administration of a small number of polyclonal CD4+ T cells (regulatory T cells or T-reg) belonging to either the CD4+CD25+ or the CD4+CD25- T cell subpopulations. The biological impact of T-reg administration is large, and, therefore, so is its potential for clinical application, yet many important properties of T-reg cells that control spontaneous EAE remain poorly understood. This application focuses on key events involved in immunoregulation of spontaneous EAE in MBP-specific T cell receptor transgenic mice. In Aim 1, we will assess the role of the cytokines, cytokine receptors and co-stimulatory molecules IL-2, CD25, IL-10, TGF-b and CD28 in the generation, survival and function of T-reg. A better knowledge of T-reg dependence on these cytokines and co-stimulatory signals may enhance the potential of in vivo manipulation of immunoregulatory T cells. In Aim 2, we will investigate the MHC restriction of regulatory T cells. The characteristics of MHC restriction of T-reg cells may help in the design of strategies to purify these cells out of the total CD4+ T cell compartment.