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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Inducible costimulator is required for type 2 antibody isotype switching but not T helper cell type 2 responses in chronic nematode infection
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Inducible costimulator is required for type 2 antibody isotype switching but not T helper cell type 2 responses in chronic nematode infection

机译：慢性线虫感染中2型抗体同种型转换需要诱导性共刺激物，但2型T辅助细胞不需要

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摘要

Inducible costimulator (ICOS) has been suggested to perform an important role in T helper cell type 2 (Th2) responses, germinal center formation, and isotype switching. The role of ICOS in chronic Th2 responses was studied in a nematode model with the filarial parasite, Brugia malayi. Contrary to expectations, we did not observe a significant defect in IL-4-producing Th2 cells in ICOS-/- mice or in eosinophil recruitment. We also found that ICOS was not required for the differentiation of alternatively activated macrophages (AAM Phi) that express Ym1 and Fizz1. Although the production of IgE was slightly reduced in ICOS-/- mice, this was not as significant as in CD28-/- mice. In contrast to live infection, the primary response of ICOS-/- mice immunized with soluble B. malayi antigen and complete Freund's adjuvant resulted in significantly fewer IL-4-producing cells in the lymph nodes. As previously reported, we observed a defect in antibody isotype switching toward the IgG1 isotype in ICOS-/- mice during live infection. Interestingly, there was a significant enhancement of parasite-specific IgG3 isotype antibodies. CD28-/- and MHC class II-/mice also had enhanced parasite-specific IgG3 isotype antibodies. Our results suggest that ICOS is not required to maintain a chronic cellular Th2 response. The primary role of ICOS in a chronic helminth infection could be to drive antibodies toward type 2 isotypes. T-independent antibody response to the parasite could be enhanced in the absence of costimulation and T cell help.
机译：有人建议诱导型共刺激物（ICOS）在T型辅助细胞2型（Th2）应答，生发中心形成和同型转换中起重要作用。在带有丝状寄生虫马来虫的线虫模型中研究了ICOS在慢性Th2反应中的作用。与预期相反，我们未在ICOS-/-小鼠或嗜酸性粒细胞募集中观察到产生IL-4的Th2细胞有明显缺陷。我们还发现，表达Ym1和Fizz1的交替激活的巨噬细胞（AAM Phi）的分化不需要ICOS。尽管在ICOS-/-小鼠中IgE的产生略有减少，但这并不像在CD28-/-小鼠中那么重要。与活感染相反，用可溶性马来芽孢杆菌抗原和完全弗氏佐剂免疫的ICOS-/-小鼠的主要应答导致淋巴结中产生IL-4的细胞明显减少。如先前报道，我们观察到在活感染过程中，ICOS-/-小鼠中抗体同种型向IgG1同种型转换的缺陷。有趣的是，寄生虫特异性IgG3同种型抗体显着增强。 CD28-/-和MHC II类//小鼠也具有增强的寄生虫特异性IgG3同种型抗体。我们的结果表明，不需要ICOS来维持慢性细胞Th2反应。 ICOS在慢性蠕虫感染中的主要作用可能是将抗体推向2型同种型。在没有共同刺激和T细胞帮助的情况下，可以增强对寄生虫的T非依赖性抗体应答。

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