Chen S S, Stanescu G, Magalski A E, Qian Y Y
Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106.
J Immunol. 1989 Jun 15;142(12):4225-32.
Cyclosporin A (CsA) is an undecapeptide fungal metabolite and is generally regarded as a new generation of immunosuppressive drugs. We uncovered a novel immunomodulatory property of CsA as a potent immunologic stimulator in the murine IgE antibody system. The enhancement of IgE responses was observed in mice receiving as few as three daily i.m. injections before Ag priming. Our studies demonstrate the three points listed below. First, CsA potentiates murine IgE responses regardless of Ag specificities in inbred mice. A hierarchy of immunopotentiation by CsA follows the order of low, intermediate, and high IgE responder mice. Second, CsA, when administered along with Ag, exerts a thorough and long lasting impact on the Ag-specific IgE antibody response, and leads to an Ag-specific breakthrough of IgE antibody synthesis in mice rendered tolerant in the IgE antibody system by soluble Ag pretreatment or neonatal IgE treatment. Third, IgE enhancer cells become sensitive to a low dose of irradiation. Two enhancer cellular components are identified, those of the Th cells and B cells, which appear to favor the induction of IgE responses. Understanding the cellular basis of the immunopotentiating effect of CsA will provide further insight into the murine IgE antibody system.
环孢素A(CsA)是一种十一肽真菌代谢产物,通常被视为新一代免疫抑制药物。我们发现CsA在小鼠IgE抗体系统中作为一种有效的免疫刺激剂具有一种新的免疫调节特性。在抗原致敏前,每天仅进行三次肌肉注射的小鼠中就观察到了IgE反应的增强。我们的研究证明了以下三点。第一,在近交系小鼠中,无论抗原特异性如何,CsA都能增强小鼠的IgE反应。CsA免疫增强的等级顺序为低、中、高IgE反应小鼠。第二,当CsA与抗原一起给药时,它对抗原特异性IgE抗体反应产生全面而持久的影响,并导致通过可溶性抗原预处理或新生儿IgE治疗在IgE抗体系统中产生耐受的小鼠中出现抗原特异性的IgE抗体合成突破。第三,IgE增强细胞对低剂量辐射变得敏感。确定了两种增强细胞成分,即Th细胞和B细胞的成分,它们似乎有利于IgE反应的诱导。了解CsA免疫增强作用的细胞基础将为深入了解小鼠IgE抗体系统提供进一步的见解。