CHEMOKINES AND AUTOIMMUNE ENCEPHALOMYELITIS

性状（改编自研究者摘要）：蛋白脂质蛋白 (PLP)是髓磷脂的主要成分，似乎是 实验性自身免疫性脑脊髓炎（EAE） 多发性硬化症（MS）慢性复发性EAE是在 通过用完整PLP或免疫显性PLP免疫SJL/J小鼠， 表位（PLP 139 -151）。过继性转移也可诱发EAE 对PLP或PLP 139 -151特异的T细胞。复发缓解型 病程如下，其临床特征为 一种以尾音消失开始的麻痹， 表现为严重的后肢无力组织学上， 中枢神经系统血管周围单核细胞浸润 (CNS)由巨噬细胞和淋巴细胞组成的白色物质， 知道了也可以看到急性和慢性脱髓鞘的区域。 由于组织学和临床疾病的相似性， EAE被认为是一种极好的动物模型， 人类脱髓鞘疾病趋化因子是小分子量 对白细胞具有趋化特性的细胞因子。一些 趋化因子如巨噬细胞炎性蛋白（MIP）-1a、MIP-1b和 单核细胞趋化蛋白（MCP）-1优先趋化 淋巴细胞和巨噬细胞。调查人员将处理 MIP-1、MIP-1b和MCP-1在急性和慢性炎症发展中的作用 主动免疫或过继免疫诱发的复发性EAE PLP/PLP 139 -151特异性T细胞的转移。这将包括 检测细胞特异性的时间趋化因子（MIP-1a，MIP-1b和MIP-1c）， MCP-1）mRNA表达和蛋白质产生，以及 外周淋巴样部位;使用体内抗体耗竭 趋化因子和评估对急性和复发性EAE的影响， 临床和组织学疾病的术语;并确定 趋化因子对单核细胞亚群浸润到CNS中的影响 在EAE的急性和复发过程中。的作用 趋化因子在PLP 139 -151特异性T细胞浸润到 将探索CNS和外周免疫T细胞应答。

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.