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 中枢神经系统疾病(CNS)作为多发性脑脊髓炎模型研究 硬化症。携带髓鞘碱性蛋白(MBP)特异性单克隆化的小鼠 AB T细胞亚群自发发生EAE。可以在以下方面预防EAE 这些小鼠通过注射少量的多克隆CD4+T细胞 (调节性T细胞或T-reg)属于CD4+CD25+或 CD4+CD25-T细胞亚群。T-reg给药的生物学影响 是巨大的，因此，它的临床应用潜力也很大，但许多 控制自发性EAE的T-reg细胞的重要特性仍然很差 明白了。此应用程序重点关注 自发性EAE对MBP特异性T细胞受体的免疫调节作用 转基因小鼠。在目标1中，我们将评估细胞因子、细胞因子的作用 IL-2、CD25、IL-10、转化生长因子-β和CD28受体及共刺激分子 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 体内操作免疫调节性T细胞的可能性。在目标2中，我们将 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CD4+T细胞隔间中取出。

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.