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将来自经鼻内卵清蛋白免疫小鼠的T细胞转移至卵清蛋白致敏的受体小鼠中可改善过敏反应。

Transfer of T cells from intranasal ovalbumin-immunized mice ameliorates allergic response in ova-sensitized recipient mice.

作者信息

Akkoc Tunc, Eifan Aarif O, Aydogan Metin, Ozkara Selvinaz, Bahceciler Nerin N, Barlan Isil B

机构信息

Pediatric Department, Faculty of Medicine, Division of Pediatric Allergy and Clinical Immunology, Marmara University, Istanbul, Turkey.

出版信息

Allergy Asthma Proc. 2008 Jul-Aug;29(4):411-6. doi: 10.2500/aap.2008.29.3106. Epub 2008 Mar 13.

Abstract

Mucosal immunotherapy is suggested as a treatment strategy for tolerance induction in allergic diseases. The purpose of this study was to determine the effect of transferred splenic T cells from intranasal ovalbumin (OVA)-immunized mice to naive mice before sensitization on its impact of cytokine production and airway histopathology. BALB/c mice in group I received intranasal immunotherapy (days1-6), carboxylfluorescein succinyl ester (CFSE)-labeled splenocytes or splenic T cells were i.v. transferred to naive recipients (group II) before OVA sensitization. Acute murine asthma model was established by two i.p. OVA injections (days 21 and 28) and seven OVA nebulizations (days 42-48) in groups I, II and III. Groups III and IV served as asthma model and control, respectively. CFSE-labeled cells in splenocytes and lymph node lymphocytes, lung histopathology, IL-4, IL-10, and interferon (IFN) gamma cytokines of recipients were analyzed 24 hours after OVA nebulization challenge. CFSE-labeled T cells from group I were detected in spleen and regional lymph nodes of the OVA-sensitized recipients (group II). Smooth muscle and thickness of airways were less in intranasal OVA immunotherapy and OVA-sensitized recipients when compared with the asthma model (p < 0.05). Area of inflammation was significantly suppressed in OVA-sensitized recipients compared with the asthma model (p < 0.01). IL-10 and IFN-gamma levels in splenocyte supernatants were significantly increased in intranasal immunotherapy and OVA-sensitized recipients compared with asthma model and controls (p < 0.01). IL-4 levels were significantly less in intranasal immunotherapy group and the OVA-sensitized recipient group when compared with asthma the model group (p < 0.05). This study suggests that intranasal immunotherapy with allergens regulates T-cell responses and ameliorates airway histopathology in sensitized mice, hence, encouraging mucosal tolerance induction as a suitable treatment of allergic diseases.

摘要

黏膜免疫疗法被认为是诱导过敏性疾病产生耐受性的一种治疗策略。本研究的目的是确定在致敏前将经鼻内卵清蛋白(OVA)免疫的小鼠的脾T细胞转移至未致敏小鼠对细胞因子产生及气道组织病理学的影响。第一组BALB/c小鼠接受鼻内免疫疗法(第1 - 6天),在OVA致敏前,将羧基荧光素琥珀酰亚胺酯(CFSE)标记的脾细胞或脾T细胞经静脉注射转移至未致敏受体(第二组)。通过腹腔注射两次OVA(第21天和第28天)以及对第一、二、三组进行七次OVA雾化(第42 - 48天)建立急性小鼠哮喘模型。第三组和第四组分别作为哮喘模型组和对照组。在OVA雾化激发24小时后,分析受体脾细胞和淋巴结淋巴细胞中CFSE标记的细胞、肺组织病理学、白细胞介素-4(IL-4)、白细胞介素-10(IL-10)和干扰素(IFN)γ细胞因子。在OVA致敏受体(第二组)的脾脏和局部淋巴结中检测到来自第一组的CFSE标记的T细胞。与哮喘模型相比,经鼻内OVA免疫疗法和OVA致敏受体的气道平滑肌和厚度更小(p < 0.05)。与哮喘模型相比,OVA致敏受体的炎症面积明显受到抑制(p < 0.01)。与哮喘模型组和对照组相比,经鼻内免疫疗法和OVA致敏受体的脾细胞上清液中IL-10和IFN-γ水平显著升高(p < 0.01)。与哮喘模型组相比,经鼻内免疫疗法组和OVA致敏受体组的IL-4水平显著降低(p < 0.05)。本研究表明,用变应原进行鼻内免疫疗法可调节T细胞反应并改善致敏小鼠的气道组织病理学,因此,鼓励将黏膜耐受性诱导作为过敏性疾病的一种合适治疗方法。

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