THERAPEUTIC VACCINATION AGAINST ADJUVANT ARTHRITIS USING AUTOIMMUNE T-CELLS TREATED WITH HYDROSTATIC-PRESSURE
THERAPEUTIC VACCINATION AGAINST ADJUVANT ARTHRITIS USING AUTOIMMUNE T-CELLS TREATED WITH HYDROSTATIC-PRESSURE
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DOI：
10.1073/pnas.84.13.4577
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发表时间：
1987-07-01
影响因子：
11.1
通讯作者：
COHEN, IR
中科院分区：
文献类型：
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作者：
LIDER, O;KARIN, N;COHEN, IR
自身免疫性疾病的理想治疗方法将是特异性中和导致疾病的自身反应性淋巴细胞的无毒手段。这一目标已经在实验性自身免疫模型中实现，通过使大鼠或小鼠针对其自身的自身免疫细胞免疫，使得动物产生特异性抑制致病淋巴细胞的免疫应答。这种策略，称为淋巴细胞接种，被证明是有效的，使用一些，但不是全部，自身免疫辅助T淋巴细胞系。我们现在报告说，T淋巴细胞，否则不能触发免疫反应，可以转化为有效的免疫原，通过处理细胞在体外与静水压力。克隆A2b就是这样一种细胞，它作为一种效应克隆，能识别软骨蛋白聚糖并在刘易斯大鼠中引起佐剂性关节炎。未经治疗的A2b不能引发免疫反应，但用抗独特型A2b治疗的大鼠诱导了已建立的佐剂性关节炎的早期缓解以及对随后疾病的抵抗。对关节炎的特异性抗性与对克隆A2b的抗独特型T细胞反应性相关，并且可以使用供体淋巴样细胞从接种疫苗的大鼠转移到幼稚受体。聚集的T淋巴细胞膜comonents似乎是重要的免疫反应，因为静水压力的影响，可以通过处理A2b与化学交联剂或与破坏细胞骨架的代理再现。来自抗原致敏大鼠的淋巴结细胞群体，当用静水压力处理时，也可以诱导疾病的抑制。因此，可以开发有效的疫苗，而不必将自身免疫T淋巴细胞分离为细胞系或克隆。这些结果表明，经适当处理的效应T淋巴细胞可用作特异性控制免疫系统的试剂。
An ideal treatment for autoimmune diseases would be a nontoxic means of specifically neutralizing the autoreactive lymphocytes responsible for the disease. This goal has been realized in experimental autoimmunity models by immunizing rats or mice against their own autoimmune cells such that the animals generate an immune response specifically repressive to the disease-producing lymphocytes. This maneuver, termed lymphocyte vaccination, was demonstrated to be effective using some, but not all, autoimmune helper T lymphocyte lines. We now report that T lymphocytes, otherwise incapable of triggering an immune response, can be transformed into effective immunogens by treating the cells in vitro with hydrostatic pressure. Clone A2b, as effector clone that recognized cartilage proteoglycan and caused adjuvant arthritis in Lewis rats, is such a cell. Untreated A2b could not trigger an immune rsponse, but inoculating rats with anti-idiotypic A2b induced early remission of established adjuvant arthritis as well as resistance to subsequent disease. Specific resistance to arthritis was associated with anti-idiotypic T-cell reactivity to clone A2b and coudl be transferred from vaccinated rats to naive recipients using donor lymphoid cells. Aggregation of T-lymphocyte membrane comonents appeared to be important for an immune response because the effects of hydrostatic pressure could be reproduced by treatment of A2b with chemical cross-linkers or with agents disrupting the cytoskeleton. Populations of lymph node cells from antigen-primed rats, when treated with hydrostatic pressure, could also induce suppression of disease. Thus, effective vaccines can be developed without having to isolate the autoimmune T lymphocytes as lines or clones. These results demonstrate that effector T lymphocytes suitably treated may serve as agents for specifically controlling the immune system.