Charaterizing lymphocytes that suppress Experimental Autoimmune Encephalomyelitis

描述（由申请人提供）：实验性自身免疫性脑脊髓炎是一种中枢神经系统（CNS）的炎症性脱髓鞘疾病，作为多发性硬化症的模型研究。携带单克隆髓鞘碱性蛋白（MBP）特异性抗体T细胞室的小鼠会自发发生EAE。在这些小鼠中，通过给予少量属于CD4+CD25+或CD4+CD25- T细胞亚群的多克隆CD4+ T细胞（调节性T细胞或T-reg）可以预防EAE。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是巨大的，然而控制自发性EAE的T-reg细胞的许多重要特性仍然知之甚少。本应用程序主要关注mbp特异性T细胞受体转基因小鼠自发性EAE免疫调节的关键事件。在Aim 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、CD25、IL-10、TGF-b和CD28在T-reg的产生、存活和功能中的作用。更好地了解T-reg对这些细胞因子和共刺激信号的依赖性，可能会增强体内操纵免疫调节性T细胞的潜力。在目标2中，我们将研究调节性T细胞的MHC限制。T-reg细胞的MHC限制特性可能有助于设计将这些细胞从总CD4+ T细胞区室中纯化出来的策略。

DESCRIPTION (provided by applicant): 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.