Peripheral tolerance of antigen-specific Th cells induced with polyethylene glycol-conjugate of protein antigen
Peripheral tolerance of antigen-specific Th cells induced with polyethylene glycol-conjugate of protein antigen
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蛋白抗原聚乙二醇缀合物诱导抗原特异性 Th 细胞的外周耐受
DOI：
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
H. Nishimura
中科院分区：
文献类型：
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作者：
M. Obata;T. Fujii;M. Ohtsuji;Y. Kodera;H. Nishimura
蛋白抗原与聚乙二醇偶联物(聚乙二醇，一种非免疫原性人工聚合物)可诱导抗原特异性Th细胞产生免疫耐受。然而，这种耐受诱导的机制仍然不清楚。本研究研究了卵清蛋白(OVA)特异性的CD4+Th细胞在可耐受的聚乙二醇卵蛋白(PEGOVA)结合物(PEGOVA)作用下的反应和分化。用羧基荧光素琥珀酰亚胺酯(CFSE)标记OT-II小鼠的NAVE OVA特异性Th细胞，转移到组织相容的C57BL/6小鼠，然后用耐受性的聚乙二醇OVA或OVA刺激。在体内用耐受性的聚乙二醇卵蛋白刺激时，这些细胞表现出与用卵蛋白刺激所观察到的类似的强劲的增殖反应。然而，当长时间暴露于PEGOVA时，OVA特异性Th细胞变得无能，在体外用抗原性OVA323-339肽刺激时，其反应能力和产生IL-2和其他细胞因子的能力显著降低。经PEGOVA处理后，OT-II小鼠脾中TCRVCD2+α+T细胞的克隆率也显著降低。天然OVA特异性Th细胞在持续暴露于PEGOVA后的这些反应特征与报道的将相同细胞转入系统表达转基因OVA基因的小鼠非常相似。观察到的聚乙二醇卵蛋白在循环中的高度稳定性可能是其耐受性的基础。
It has long been known that protein antigen conjugated with polyethylene glycol (PEG), a nonimmunogenic artificial polymer, induces immune tolerance of antigen-specific Th cells. However, the mechanism of this tolerance induction remains unknown. In this study, the response and differentiation of ovalbumin (OVA)-specific CD4+ Th cells upon exposure to tolerogenic PEG conjugate of OVA (PEG-OVA) were studied. Na?ve OVA-specific Th cells from OT-II mice were labeled with carboxyfluorescein succinimidyl ester (CFSE), transferred into histocompatible C57BL/6 mice, and then subsequently stimulated with either tolerogenic PEG-OVA or with OVA. Upon stimulation with tolerogenic PEG-OVA in vivo, these cells showed a robust proliferative response comparable to that observed by stimulation with OVA. Nevertheless, upon prolonged exposure to PEG-OVA, OVA-specific Th cells became anergic, showing a markedly reduced capacity to respond, and to produce IL-2 and other cytokines when stimulated with antigenic OVA323-339 peptide in vitro. There was also a significant reduction of the frequency of clonotypic TCR Vα2+CD4+ T cells in the spleens of OT-II mice treated with PEG-OVA. These features of response of na?ve OVA-specific Th cells upon sustained exposure to PEG-OVA were quite analogous to those reported for the same cells transferred into mice with systemic expression of the transgenic OVA gene. The highly enhanced stability in the circulation that was observed for PEG-OVA was likely the basis of its tolerogenic capacity.
影响因子：
2.9
作者：
McFarland, BJ;Sant, AJ;Beeson, C
通讯作者：
Beeson, C