Kinetics of IL-17-and interferon-γ-producing PLPp-specific CD4 T cells in EAE induced by coinjection of PLPp/IFA with pertussis toxin in SJL mice
Kinetics of IL-17-and interferon-γ-producing PLPp-specific CD4 T cells in EAE induced by coinjection of PLPp/IFA with pertussis toxin in SJL mice
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DOI：
10.1016/j.neulet.2010.04.018
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发表时间：
2010-06-07
影响因子：
2.5
通讯作者：
Forsthuber, Thomas G.
中科院分区：
文献类型：
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作者：
Hofstetter, Harald H.;Forsthuber, Thomas G.
百日咳毒素（PTX）的全身给药消除了由注射在不完全弗氏佐剂（IFA）中的神经抗原介导的T细胞耐受，并引起实验性自身免疫性脑脊髓炎（EAE）。紫杉醇同时诱导高频率的神经抗原特异性和产生IL-17的T细胞。IL-17和IFN-γ都是EAE发病机制中的关键效应细胞因子，可能具有不同的功能。因此，我们研究了PTX诱导的神经抗原特异性IFN-γ和IL-17产生的T细胞效应物群体的时间和空间动力学的潜在差异。产生IFN-γ和IL-17的PLP β特异性T细胞最初在免疫后以可比的频率在局部引流淋巴结（drLN）中出现，如通过细胞因子ELISPOT测量的。高频率的IFN-γ和IL-17产生的T细胞存在于EAE发病前的免疫外周。在急性EAE期间，PTX诱导的产生IFN-γ和IL-17的PLPp特异性细胞的最高频率在发炎的CNS中一致。在恢复期间，产生IFN-γ和IL-17的PLPp特异性T细胞同时从CNS消失，而这些细胞的高频率仍然存在于免疫外周中。IFN-γ和IL-17产生T细胞的功能亲和力在EAE期间没有改变。因此，该模型中的自身免疫病理学与Th 1或Th 17细胞的动力学和CNS迁移方面的特异性PTX作用无关。(C)2010年由Elsevier爱尔兰有限公司出版。
Systemic administration of Pertussis toxin (PTX) abrogates T cell tolerance mediated by injection of neuroantigens in incomplete Freund's adjuvant (IFA) and causes experimental autoimmune encephalomyelitis (EAE). PTX concomitantly induces high frequencies of neuroantigen-specific and IL-17-producing T cells. Both IL-17 and IFN-gamma have been implicated as a key effector cytokines in the pathogenesis of EAE, possibly with different functions. We therefore investigated potential differences in the temporal and spatial kinetics of the PTX-induced neuroantigen-specific IFN-gamma- and IL-17-producing T cell effector populations. IFN-gamma- and IL-17-producing PLPp-specific T cells initially arose in comparable frequencies in the local draining lymph nodes (drLN) after immunization as measured by cytokine ELISPOT. High frequencies of both IFN-gamma- and IL-17-producing T cells were present in the immune periphery before onset of EAE. The highest frequencies of PTX-induced IFN-gamma- and IL-17-producing PLPp-specific cells coincided in the inflamed CNS during acute EAE. During recovery, both IFN-gamma- and IL-17-producing PLPp-specific T cells simultaneously disappeared from the CNS, whereas high frequencies of these cells remained present in the immune periphery. The functional affinity of both IFN-gamma- and IL-17-producing T cells did not change during EAE. Therefore, autoimmune pathology in this model did not correlate with specific PTX effects either on Th1 or Th17 cells regarding their kinetics and CNS migration. (C) 2010 Published by Elsevier Ireland Ltd.