Pertussis toxin modulates the immune response to neuroantigens injected in incomplete Freund's adjuvant: Induction of Th1 cells and experimental autoimmune encephalomyelitis in the presence of high frequencies of Th2 cells
Pertussis toxin modulates the immune response to neuroantigens injected in incomplete Freund's adjuvant: Induction of Th1 cells and experimental autoimmune encephalomyelitis in the presence of high frequencies of Th2 cells
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DOI：
10.4049/jimmunol.169.1.117
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发表时间：
2002-07-01
影响因子：
4.4
通讯作者：
Forsthuber, TG
中科院分区：
文献类型：
--
作者：
Hofstetter, HH;Shive, CL;Forsthuber, TG
百日咳毒素（PT）已被广泛用于促进啮齿动物实验性自身免疫性脑脊髓炎（EAE）的诱导。有人认为，这种微生物产品通过打开血脑屏障来促进 EAE，从而促进致病性 T 细胞迁移至中枢神经系统。然而，PT 具有其他生物学效应，可能有助于其在 EAE 中的活性，例如增强 T 细胞产生细胞因子和诱导淋巴细胞增多。在这项工作中，我们研究了 PT 对小鼠 EAE 中神经抗原反应性 T 细胞的致病性、细胞因子分化和克隆大小的影响。我们的结果表明，PT 阻止了在 IFA 中注射 PLPp139-151 所带来的 EAE 保护，并诱导高频率的肽特异性 Th1 细胞和疾病。有趣的是，尽管 PLPp139 -151 特异性 Th2 细胞同时进行了剧烈的克隆扩增，但小鼠仍出现了 EAE。数据表明，该模型中的 Th2 细胞既不能预防 EAE，也不能促进该疾病。此外，结果表明，PT 诱导的淋巴组织和中枢神经系统中 APC 的激活促进了毒素对神经抗原反应性 T 细胞的影响。总之，结果表明，微生物产物，如 PT，可能通过调节先天性免疫系统和适应性免疫系统之间对自身 Ag 的反应而导致自身免疫性疾病的发生。
Pertussis toxin (PT) has been widely used to facilitate the induction of experimental autoimmune encephalomyelitis (EAE) in rodents. It has been suggested that this microbial product promotes EAE by opening up the blood-brain barrier and thereby facilitates the migration of pathogenic T cells to the CNS. However, PT has other biological effects that could contribute to its activity in EAE, such as enhancing the cytokine production by T cells and induction of lymphocytosis. In this work, we investigated the effects of PT on the pathogenicity, cytokine differentiation, and clonal sizes of neuroantigen-reactive T cells in EAE in mice. Our results show that PT prevented the protection from EAE conferred by injection of PLPp139-151 in IFA and induced high frequencies of peptide-specific Th1 cells and disease. Interestingly, the mice developed EAE despite the simultaneous vigorous clonal expansion of PLPp139 -151-specific Th2 cells. The data indicate that the Th2 cells in this model neither were protective against EAE nor promoted the disease. Furthermore, the results suggested that the effects of the toxin on neuroantigen-reactive T cells were promoted by the PT-induced activation of APCs in lymphoid tissues and the CNS. Together, the results suggest that microbial products, such as PT, could contribute to the initiation of autoimmune disease by modulating the interaction between the innate and adaptive immune system in the response to self Ags.