Basophils Can Directly Present or Cross-Present Antigen to CD8 Lymphocytes and Alter CD8 T Cell Differentiation into IL-10-Producing Phenotypes

Basophils Can Directly Present or Cross-Present Antigen to CD8 Lymphocytes and Alter CD8 T Cell Differentiation into IL-10-Producing Phenotypes
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DOI:
10.4049/jimmunol.0900332
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发表时间:
2009-09-01
影响因子:
4.4
通讯作者:
Min, Booki
Min, Booki
中科院分区:
医学2区
文献类型:
--
作者:
Kim, Sohee;Shen, Tao;Min, Booki

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越来越多的证据表明,嗜碱性粒细胞在体外和体内Th 2型免疫中发挥关键作用。我们以前报道过嗜碱性粒细胞与抗原刺激的初始CD 4 T细胞共培养可促进T细胞分化为产生IL-4的Th 2细胞。在本研究中,我们研究了嗜碱性粒细胞在CD 8 T细胞活化过程中的作用。虽然用OVA肽脉冲的脾树突状细胞刺激OVA特异性OT-I CD 8 T细胞主要诱导IFN-γ的产生,但向共培养物中加入嗜碱性粒细胞诱导IL-10的产生。令人惊讶的是,嗜碱性粒细胞能够直接呈递肽Ag或交叉呈递蛋白Ag到CD 8 T细胞。CD 28介导的共刺激显著增强T细胞IL-10的产生,但ICOS和CD 86均不参与IL-10的产生。在没有IL-4或IL-6的情况下,嗜碱性粒细胞介导的IL-10诱导大大减少,表明这些细胞因子是编程CD 8 T细胞IL-10产生所必需的。将IL-4或IL-6加入到CD 8/APC共培养物中不足以诱导IL-10的产生;然而,两种细胞因子的存在显著诱导了IL-10的产生,而没有嗜碱性粒细胞。最后,由嗜碱性粒细胞诱导的产生IL-10的CD 8 T细胞不显示调节细胞功能。总的来说,这些结果表明嗜碱性粒细胞作为专业APC将Ag呈递给CD 8 T细胞,从而诱导IL-10产生的新功能。免疫学杂志,2009,183:3033-3039.
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-p resenting 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. The Journal of Immunology, 2009, 183: 3033-3039.