Differential properties of peripheral versus central nervous system (CNS) antigen-presenting cells: relevance for antigen-presenting cell T cell interactions and implications for the pathogenesis and therapy of CNS inflammation

外周与中枢神经系统 (CNS) 抗原呈递细胞的差异特性：与抗原呈递细胞 T 细胞相互作用的相关性以及对 CNS 炎症发病机制和治疗的影响

• 批准号: 5436176
• 负责人: Dr. Bettina Schreiner
• 金额: --
• 依托单位: Montreal Neurological Institute-Hospital
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5436176?language=en
• 关键词: Differential; properties; peripheral; versus; central

Antigen presentation in the CNS is thought to play a critical role in the initiation and perpetuation of neuroinflammation. It is becoming apparent that microglial cells differ considerably from peripheral antigen-presenting cells in terms of their responses to inflammatory stimuli and their abilities to modulate immune responses. The proposed project aims at defining the relevant functional differences that exist between professional antigen-presenting cells in the periphery (monocytes, B cells, differentially matured dendritic cells) versus microglial cells with respect to their contributions to CNS inflammation. The project includes the investigation of how autologous and potentially autoreactive T cell activation is controlled or modulated by peripheral versus CNS antigenpresenting cells and how these findings might be relevant for the immunopathogenesis and the therapy of multiple sclerosis. Special consideration is given to how these differences might impact the steps of disease initiation, propagation and chronicity. Specifically, differences between the expression and regulation of the MHC class 11 antigen-processing machinery, novel members of the B7 family members of costimulatory molecules (B7-H2 (ICOS-L)/ICOS, B7-Hl (PD-L1)/PD-1non-PD-1, B7-DC (PD-L2)/PD1-non-PD1, B7-H3/X, B7-H4 (B7HSl)/BTLA-4), members of the immunoglobulin family and non-classical MHC molecules on distinct antigen-presenting cell subsets will be studied.

中枢神经系统中的抗原呈递被认为在神经炎症的引发和持续中发挥着关键作用。越来越明显的是，小胶质细胞在对炎症刺激的反应和调节免疫反应的能力方面与外周抗原呈递细胞有很大不同。该项目旨在明确外周专业抗原呈递细胞（单核细胞、B 细胞、不同成熟的树突状细胞）与小胶质细胞之间存在的相关功能差异，这些差异对中枢神经系统炎症的贡献有关。该项目包括研究外周抗原呈递细胞与中枢神经系统抗原呈递细胞如何控制或调节自体和潜在自身反应性 T 细胞激活，以及这些发现如何与免疫发病机制和多发性硬化症的治疗相关。特别考虑这些差异如何影响疾病的发生、传播和慢性化的步骤。具体而言，MHC 11类抗原加工机器、共刺激分子的B7家族成员的新成员（B7-H2 (ICOS-L)/ICOS、B7-Hl (PD-L1)/PD-1non-PD-1、B7-DC (PD-L2)/PD1-non-PD1、B7-H3/X、B7-H4的表达和调节之间的差异 (B7HS1)/BTLA-4)、免疫球蛋白家族的成员和不同抗原呈递细胞亚群上的非经典MHC分子将被研究。