Accessory cell function of human eosinophils. HLA-DR-dependent, MHC-restricted antigen-presentation and IL-1 alpha expression.

Accessory cell function of human eosinophils. HLA-DR-dependent, MHC-restricted antigen-presentation and IL-1 alpha expression.
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DOI:
10.4049/jimmunol.150.6.2554
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发表时间:
1993-03
影响因子:
4.4
通讯作者:
P. Weller;T. H. Rand;T. Barrett;A. Elovic;David T. W. Wong;R. Finberg
P. Weller;T. H. Rand;T. Barrett;A. Elovic;David T. W. Wong;R. Finberg
中科院分区:
医学2区
文献类型:
--
作者:
P. Weller;T. H. Rand;T. Barrett;A. Elovic;David T. W. Wong;R. Finberg

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尽管外周血嗜酸性粒细胞表达很少的II类MHC蛋白HLA-DR,但嗜酸性粒细胞可以通过暴露于细胞因子(包括粒细胞-巨噬细胞-CSF、IL-4和IFN-γ)而被诱导表达HLA-DR,其中粒细胞-巨噬细胞-CSF引发最高水平的HLA-DR表达,如通过流式细胞术评估的。HLA-DR+嗜酸性粒细胞作为APC发挥功能的能力用不含单核细胞的血液嗜酸性粒细胞进行评价,用粒细胞-巨噬细胞-CSF培养以诱导HLA-DR表达,然后暴露于Ag破伤风类毒素。HLA-DR+嗜酸性粒细胞与多聚甲醛固定后,银曝光刺激T细胞增殖,而HLA-DR+嗜酸性粒细胞与多聚甲醛固定前,银曝光不能刺激淋巴细胞增殖。抗HLA-DR单克隆抗体可抑制Ag脉冲刺激的HLA-DR+嗜酸性粒细胞诱导的淋巴细胞增殖反应,且仅限于HLA-DR相容性淋巴细胞。此外,从嗜酸性粒细胞增多供体的嗜酸性粒细胞,无论是之前和更显着的PMA刺激后,包含IL-1-α mRNA的转录本可检测的北方印迹杂交和原位杂交和表达IL-1-α蛋白可检测的免疫组织化学。这些发现表明,人嗜酸性粒细胞可以处理Ag,表达共刺激细胞因子IL-1-α,并在马槟榔引起的HLA-DR表达诱导后,可以作为HLA-DR依赖性的MHC限制性APC刺激T淋巴细胞应答。
Although peripheral blood eosinophils express little of the class II MHC protein, HLA-DR, eosinophils could be induced to express HLA-DR by exposures to cytokines, including granulocyte-macrophage-CSF, IL-4, and IFN-gamma, with granulocyte-macrophage-CSF eliciting the greatest level of HLA-DR expression as assessed by flow cytometry. The capacity of HLA-DR+ eosinophils to function as APC was evaluated with blood eosinophils isolated free of mononuclear cells, cultured with granulocyte-macrophage-CSF to induce HLA-DR expression and then exposed to the Ag tetanus toxoid. HLA-DR+ eosinophils fixed with paraformaldehyde after Ag exposure stimulated T cell proliferation, whereas HLA-DR+ eosinophils fixed with paraformaldehyde before Ag exposure failed to stimulate lymphocyte proliferation. The lymphocyte proliferative responses elicited by Ag-pulsed HLA-DR+ eosinophils were inhibited by anti-HLA-DR mAb and were restricted to HLA-DR compatible lymphocytes. Moreover, eosinophils from a hypereosinophilic donor, both before and more prominently after stimulation with PMA, contained transcripts for IL-1-alpha mRNA detectable by Northern blot hybridization and in situ hybridization and expressed IL-1-alpha protein detectable by immunohistochemistry. These findings indicate that human eosinophils can process Ag, express the costimulatory cytokine IL-1-alpha, and after cytokine-elicited induction of HLA-DR expression can function as HLA-DR-dependent, MHC-restricted APC in stimulating T lymphocyte responses.