T-CELLS RESPONSIVE TO MYELIN BASIC-PROTEIN IN PATIENTS WITH MULTIPLE-SCLEROSIS
T-CELLS RESPONSIVE TO MYELIN BASIC-PROTEIN IN PATIENTS WITH MULTIPLE-SCLEROSIS
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DOI：
10.1126/science.1689076
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发表时间：
1990-02-09
期刊：
影响因子：
56.9
通讯作者：
ALBERTINI, RJ
中科院分区：
文献类型：
--
作者：
ALLEGRETTA, M;NICKLAS, JA;ALBERTINI, RJ
人类T淋巴细胞体内的基因突变似乎优先发生在分裂细胞中。多发性硬化症（MS）患者被认为具有一个或多个受到自身抗原刺激的分裂T细胞群。分离来自MS患者的突变T细胞克隆，并测试其对髓鞘碱性蛋白的反应性，髓鞘碱性蛋白是一种被认为参与疾病诱导的抗原。次黄嘌呤鸟嘌呤磷酸核糖转移酶（hprt）克隆试验用于确定突变频率值在MS患者慢性进展性疾病。11个258硫代鸟嘌呤耐药（hprt-1）T细胞克隆从五个MS患者进行了测试增殖响应人髓鞘碱性蛋白，而没有事先在体外暴露于这种抗原。没有野生型克隆从这些患者，也没有任何hprt-或野生型克隆从三个健康的人回应髓鞘碱性蛋白。因此，可以从MS患者的外周血中分离与髓鞘碱性蛋白反应的T细胞克隆。
Gene mutation in vivo in human T lymphocytes appears to occur preferentially in dividing cells. Individuals with multiple sclerosis (MS) are assumed to have one or more populations of dividing T cells that are being stimulated by autoantigens. Mutant T cell clones from MS patients were isolated and tested for reactivity to myelin basic protein, an antigen that is thought to participate in the induction of the disease. The hypoxanthine guanine phosphoribosyltransferase (hprt) clonal assay was used to determine mutant frequency values in MS patients with chronic progressive disease. Eleven of 258 thioguanine-resistant (hprt-1) T cell clones from five of the six MS patients who were tested proliferated in response to human myelin basic protein without prior in vitro exposure to this antigen. No wild-type clones from these patients, nor any hprt- or wild-type clones from three healthy individuals responded to myelin basic protein. Thus, T cell clones that react with myelin basic protein can be isolated from the peripheral blood of MS patients.