CHEMOKINES AND AUTOIMMUNE ENCEPHALOMYELITIS

描述(摘自研究人员摘要)：蛋白质脂蛋白 (PLP)是髓鞘的主要成分，似乎是 实验性自身免疫性脑脊髓炎(EAE)的免疫反应 多发性硬化症(MS)。慢性复发性EAE是由 全长PLP或免疫显性PLP免疫SJL/J小鼠 表位(PLP139-151)。领养转移也可诱发EAE PLP或PLP139-151的特异性T细胞。复发缓解期 临床上以上升为特征的病程 从尾巴失去张力开始的瘫痪，最终 表现为严重的后肢无力。从组织学上讲， 中枢神经系统血管周围单个核细胞的浸润性 (中枢神经系统)白质由巨噬细胞和淋巴细胞组成 注意到了。还可以看到急性和慢性脱髓鞘的区域。 由于在组织学和临床疾病方面的相似性 在多发性硬化症中，EAE被认为是治疗 人类脱髓鞘疾病。趋化因子是小分子的 对白细胞具有趋化性的细胞因子。一些人 趋化因子，如巨噬细胞炎症蛋白(MLP)-1a、MIP-1b和 单核细胞趋化蛋白(MCP)-1优先趋化 对于淋巴细胞和巨噬细胞。调查人员将解决 巨噬细胞趋化蛋白-1、巨噬细胞趋化蛋白-1b和单核细胞趋化蛋白-1在急性胰腺炎发生发展中的作用(S) 主动免疫或过继免疫所致的复发性EAE PLP/PLP139-151特异性T细胞的转移。这将包括 检测细胞特异性、临时性趋化因子(MLP-1a、MIP-1b和 MCP-1)在中枢神经系统中的表达和蛋白合成 外周淋巴组织部位；使用体内抗体清除 趋化因子及其对急性和复发性EAE的影响 临床和组织学疾病术语；以及确定其作用 趋化因子对单个核细胞亚群向中枢神经系统渗透的影响 在急性和复发的EAE过程中。的作用 趋化因子在PLP139-151特异性T细胞侵袭中的作用 将探索中枢神经系统和外周免疫T细胞反应。

DESCRIPTION (Adapted from Investigator's abstract): Proteolipid protein (PLP) is a major component of myelin and appears to be a target of immune responses in both experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). Chronic relapsing EAE is induced in SJL/J mice by immunization with intact PLP or the immunodominant epitope (PLP139-151). EAE can also be induced by the adoptive transfer of T-cells specific for either PLP or PLP139-151. A relapsing remitting course of disease follows that is characterized clinically by ascending paralysis that begins with loss of tail tone and eventually manifests itself as severe hind limb weakness. Histologically, perivascular mononuclear cell infiltrates of the central nervous system (CNS) white matter consisting of macrophages and lymphocytes are noted. Areas of acute and chronic demyelination can also be seen. Because of the similarities in histology and clinical disease with that seen in MS, EAE is considered an excellent animal model for human demyelinating diseases. Chemokines are small molecular weight cytokines that have chemotactic properties for leukocytes. Some chemokines such as macrophage inflammatory protein (MlP)-1a, MIP-1b, and monocyte chemotactic protein (MCP)-1 are preferentially chemotactic for Iymphocytes and macrophages. The investigators will address the role(s) of MlP-1, MIP-1b, and MCP-1 in the development of acute and relapsing EAE induced by either active immunization or adoptive transfer of PLP/PLP139-151-specific T-cells. This will include examining cell-specific, temporal chemokine (MlP-1a, MIP-1b and MCP-1) mRNA expression and protein production in the CNS as well as peripheral lymphoid sites; using in vivo antibody depletion of chemokines and assessing the effect on acute and relapsing EAE in terms of clinical and histological disease; and determining the role of chemokines on mononuclear cell subset infiltration into the CNS during the course of both acute and relapses of EAE. The role of chemokines in both the infiltration of PLP139-151-specific T-cells into the CNS and the peripheral immune T-cell response will be explored.