Escobar Alejandro, Aguirre Adam, Guzmán María Antonieta, González Rodrigo, Catalán Diego, Acuña-Castillo Claudio, Larrondo Milton, López Mercedes, Pesce Barbara, Rolland Jennifer, O'Hehir Robyn, Aguillón Juan Carlos
Research Institute of Dental Science, Faculty of Dentistry, University of Chile, Santiago, Chile.
Department of Pharmacy, Faculty of Chemistry, Catholic University of Chile, Santiago, Chile.
PLoS One. 2014 Jan 22;9(1):e85930. doi: 10.1371/journal.pone.0085930. eCollection 2014.
Natural rubber latex (NRL; Hevea brasiliensis) allergy is an IgE-mediated reaction to latex proteins. When latex glove exposure is the main sensitizing agent, Hev b 5 is one of the major allergens. Dendritic cells (DC), the main antigen presenting cells, modulated with pharmacological agents can restore tolerance in several experimental models, including allergy. In the current study, we aimed to generate DC with tolerogenic properties from NRL-allergic patients and evaluate their ability to modulate allergen-specific T and B cell responses. Here we show that dexamethasone-treated DC (dxDC) differentiated into a subset of DC, characterized by low expression of MHC class II, CD40, CD80, CD86 and CD83 molecules. Compared with LPS-matured DC, dxDC secreted lower IL-12 and higher IL-10 after CD40L activation, and induced lower alloantigenic T cell proliferation. We also show that dxDC pulsed with the dominant Hev b 5 T-cell epitope peptide, Hev b 5(46-65), inhibited both proliferation of Hev b 5-specific T-cell lines and the production of Hev b 5-specific IgE. Additionally, dxDC induced a subpopulation of IL-10-producing regulatory T cells that suppressed proliferation of Hev b 5-primed T cells. In conclusion, dxDC generated from NRL-allergic patients can modulate allergen-specific T-cell responses and IgE production, supporting their potential use in allergen-specific immunotherapy.
天然橡胶乳胶(NRL;巴西橡胶树)过敏是一种对乳胶蛋白的IgE介导反应。当接触乳胶手套是主要致敏剂时,Hev b 5是主要过敏原之一。树突状细胞(DC)作为主要的抗原呈递细胞,经药物制剂调节后可在包括过敏在内的多种实验模型中恢复免疫耐受。在本研究中,我们旨在从NRL过敏患者中生成具有致耐受性的DC,并评估其调节过敏原特异性T细胞和B细胞反应的能力。在此我们表明,地塞米松处理的DC(dxDC)分化为DC的一个亚群,其特征是MHC II类、CD40、CD80、CD86和CD83分子表达较低。与LPS成熟的DC相比,dxDC在CD40L激活后分泌较低的IL-12和较高的IL-10,并诱导较低的同种异体抗原T细胞增殖。我们还表明,用主要的Hev b 5 T细胞表位肽Hev b 5(46 - 65)脉冲处理的dxDC,可抑制Hev b 5特异性T细胞系的增殖以及Hev b 5特异性IgE的产生。此外,dxDC诱导产生了一个分泌IL-10的调节性T细胞亚群,该亚群抑制了Hev b 5致敏T细胞的增殖。总之,从NRL过敏患者中生成的dxDC可调节过敏原特异性T细胞反应和IgE产生,支持它们在过敏原特异性免疫治疗中的潜在应用。