EFFECTS OF CYCLOSPORINE-A ON HUMORAL IMMUNE-RESPONSE AND RESISTANCE AGAINST VESICULAR STOMATITIS-VIRUS IN MICE

EFFECTS OF CYCLOSPORINE-A ON HUMORAL IMMUNE-RESPONSE AND RESISTANCE AGAINST VESICULAR STOMATITIS-VIRUS IN MICE
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DOI:
10.1128/jvi.57.3.1139-1144.1986
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发表时间:
1986-03-01
影响因子:
5.4
通讯作者:
ZINKERNAGEL, RM
ZINKERNAGEL, RM
中科院分区:
医学2区
文献类型:
--
作者:
CHARAN, S;HUEGIN, AW;ZINKERNAGEL, RM

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用水泡性口炎病毒(VSV)研究了环孢素A(CS-A)对抗病毒体液应答的影响; VSV提供了同时评估T非依赖性和T依赖性抗体应答的机会。T-非依赖性抗VSV免疫球蛋白M(IgM)应答几乎不受影响,而T-依赖性初次抗VSV IgG应答被CS-A抑制;相反,二次IgG应答对CS-A高度耐药。此外,一旦发生从IgM到IgG的转换,原发性应答也变得难以被CS-A抑制。我们得出结论,CS-A对初级抗VSV抗体应答的影响是通过T依赖性机制的损害介导的;相反,记忆T细胞或记忆B细胞或两者对CS-A的抑制作用具有相当大的抗性。CS-A治疗使小鼠对VSV感染高度敏感;在CS-A治疗下,通过脚垫感染后死亡率为100%,而免疫活性小鼠存活。由于CS-A不损害早期T非依赖性抗VSV IgM中和抗体的诱导,CS-A处理小鼠的这种高死亡率说明CS-A敏感细胞在抵抗VSV中的关键作用。
The effect of cyclosporin A (CS-A) on the antiviral humoral response was studied by using vesicular stomatitis virus (VSV); VSV provided the opportunity to simultaneously assess both T-independent and T-dependent antibody responses. The T-independent anti-VSV immunoglobulin M (IgM) response was virtually unaffected, whereas the T-dependent primary anti-VSV IgG response was suppressed by CS-A; in contrast, the secondary IgG response was highly resistant to CS-A. Moreover, once the switch from IgM to IgG had occurred, the primary response also became refractory to suppression by CS-A. We concluded that the effects of CS-A on the primary anti-VSV antibody response was mediated via impairment of a T-dependent mechanim; in contrast, memory T cells or memory B cells or both were quite resistant to the suppressive effects of CS-A. CS-A treatment rendered mice highly susceptible to VSV infection; under CS-A treatment, mortality was 100% after infection via footpads, whereas immunocompetent mice survived. Since CS-A does not impair induction of early T-independent anti-VSV IgM neutralizing antibodies, this high mortality in CS-A treated mice illustrates the crucial role of CS-A-sensitive cells in resistance against VSV.