Identification of a Neuronal Immunosuppressive Protein

描述（由申请人提供）：Ntera 2/D1神经元的发育， 胚胎神经元移植治疗的替代方案， 神经功能缺损，目前在中风症状的I期试验中，导致 我们发现了一个40-60 kDA的阴离子蛋白，等电点为4.8 抑制T淋巴细胞活化，抑制 白细胞介素2（IL-2）的表达，并阻断幼稚和进行中 T淋巴细胞增殖，这不能通过补充IL-2来挽救。 初步表征表明，这种神经元衍生蛋白 代表一类新的免疫调节剂。我们建议净化和 对该蛋白质进行部分测序，在BLAST数据库中搜索序列 同源性，以确定它确实是一个独特的神经元衍生的 免疫抑制蛋白（NIP），并测试它是否废除特异性 早期和晚期T淋巴细胞mRNA和蛋白表达 激活细胞因子和细胞周期调控基因，并抑制 T淋巴细胞的效应子功能。它的鉴定将有助于 预防移植物排斥反应的治疗方法的发展 外科手术，用于治疗自身免疫，和用于预防过敏反应， 将有助于确定Ntera 2/D1神经元移植物是否同时 治疗和自我保护，并将增加我们对 神经元对中枢神经系统内免疫赦免的贡献。 拟议商业应用：不可用

DESCRIPTION (provided by applicant): Development of Ntera2/D1 neurons as an alternative to embryonic neurons for transplantation therapy to ameliorate neurological deficits, currently in a Phase I trial for stroke symptoms, led to our discovery of a 40-60 kDA anionic protein with an isoelectric point of 4.8 expressed by these neurons that inhibits T-lymphocyte activation, suppresses the expression of interleukin 2 (IL-2), and blocks both naive and ongoing T-lymphocyte proliferation, which cannot be rescued by supplemental IL-2. Preliminary characterizations suggest that this neuron-derived protein represents a novel class of immunomodulators. We propose to purify and partially sequence this protein, perform a BLAST database search for sequence homology to establish that it is indeed a unique neuron-derived immunosuppressive protein (NIP), and test whether it abrogates specific T-lymphocyte mRNA and protein expressions of early phase and late phase activation cytokines and cell cycle regulatory genes and suppresses the effector functions of T-lymphocytes. Its identification will contribute to the development of therapies for preventing graft rejection in transplantation surgeries, for treating autoimmunities, and for preventing allergic reactions, will assist in determining whether Ntera2/D1 neuronal grafts are both therapeutic and self-protective, and will add to our understanding of the neuronal contribution to immune privilege within the central nervous system. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE