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嗜碱性粒细胞可直接将抗原呈递给CD8淋巴细胞或交叉呈递抗原,并改变CD8 T细胞分化为产生白细胞介素-10的表型。

Basophils can directly present or cross-present antigen to CD8 lymphocytes and alter CD8 T cell differentiation into IL-10-producing phenotypes.

作者信息

Kim Sohee, Shen Tao, Min Booki

机构信息

Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

出版信息

J Immunol. 2009 Sep 1;183(5):3033-9. doi: 10.4049/jimmunol.0900332. Epub 2009 Aug 10.

Abstract

There is increasing evidence suggesting that basophils play a critical role in developing Th2-type immunity both in vitro and in vivo. We previously reported that basophils cocultured with naive CD4 T cells stimulated with Ag promote the differentiation of the T cells into IL-4-producing Th2 cells. In the present study, we examined the roles of basophils during CD8 T cell activation. Although stimulating OVA-specific OT-I CD8 T cells with OVA peptide-pulsed splenic dendritic cells primarily induced the production of IFN-gamma, adding basophils into the coculture induced IL-10 production. Surprisingly, basophils were capable of directly presenting peptide Ag or of cross-presenting protein Ag to CD8 T cells. CD28-mediated costimulation dramatically enhanced T cell IL-10 production, yet neither ICOS nor CD86 was involved in IL-10 production. Basophil-mediated IL-10 induction was greatly diminished without IL-4 or IL-6, indicating that these cytokines are necessary for programming CD8 T cell IL-10 production. Adding IL-4 or IL-6 into CD8/APC coculture was not sufficient to induce IL-10 production; however, the presence of both cytokines significantly induced IL-10 production without basophils. Finally, CD8 T cells producing IL-10 induced by basophils did not display regulatory cell functions. Collectively, these results suggest a novel function of basophils that act as professional APCs to present Ag to CD8 T cells, thus inducing IL-10 production.

摘要

越来越多的证据表明,嗜碱性粒细胞在体外和体内Th2型免疫的发展中发挥着关键作用。我们之前报道过,与用抗原刺激的初始CD4 T细胞共培养的嗜碱性粒细胞可促进T细胞分化为产生IL-4的Th2细胞。在本研究中,我们研究了嗜碱性粒细胞在CD8 T细胞活化过程中的作用。尽管用OVA肽脉冲的脾树突状细胞刺激OVA特异性OT-I CD8 T细胞主要诱导IFN-γ的产生,但在共培养中加入嗜碱性粒细胞可诱导IL-10的产生。令人惊讶的是,嗜碱性粒细胞能够直接向CD8 T细胞呈递肽抗原或交叉呈递蛋白抗原。CD28介导的共刺激显著增强了T细胞IL-10的产生,但ICOS和CD86均未参与IL-10的产生。没有IL-4或IL-6时,嗜碱性粒细胞介导的IL-10诱导作用大大减弱,表明这些细胞因子是编程CD8 T细胞产生IL-10所必需的。在CD8/抗原呈递细胞共培养中加入IL-4或IL-6不足以诱导IL-10的产生;然而,两种细胞因子同时存在可在没有嗜碱性粒细胞的情况下显著诱导IL-10的产生。最后,由嗜碱性粒细胞诱导产生IL-10的CD8 T细胞不表现出调节性细胞功能。总的来说,这些结果表明嗜碱性粒细胞具有一种新功能,即作为专职抗原呈递细胞向CD8 T细胞呈递抗原,从而诱导IL-10的产生。

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