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Studies on regulatory mechanism of Th1/Th2 cell differentiation by antigen presenting cell (APC) and onAPC-mediated immunotherapy

抗原呈递细胞(APC)调控Th1/Th2细胞分化的机制及APC介导的免疫治疗研究

基本信息

批准号：
16208031
负责人：
ONO Kenichiro
金额：
$ 31.87万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

项目摘要

Regulatory mechanisms of Th1/Th2 cell differentiation by antigen presenting cell (APC) and APC-mediated immunotherapy were investigated for 3 years (from 2004 to 2007) and following results were obtained.1) Th1/Th2 cell differentiation in certain diseases, such as murine babesiosis, and canine malignant melanoma and histiocytic sarcoma:a) IL-12p70 production from APC (included splenic macrophages) induced Th1 cell differentiation and closely related to transient parasitemia in Babesia microti infection. IL-12p70 was suggested to be an important factor for eliminating Babesia microti.b) Seven novel cell lines from canine histiocytic sarcoma were established. All of them showed phagocytic and processing activities, suggesting to be a mononuclear phagocytic system cell and also APC.2) Stimulatory factors for Th1/Th2 cell differentiation:a) Stimulatory factors for IL-12 production, by which Th1 cell differentiation was introduced, from macrophages were isolated and purified from culture medium of Babesia microti and Babesia rodhaini infected erythrocytes. These factors were heat stable and soluble and their elution profiles were quite different between Babesia microti and Babesia rodhaini cultured medium.3) APC-mediated immunotherapya) Against canine malignant melanoma: Canine APC from bone marrow were pulsed with lysate o canine melanoma cell lines and were transplanted into clinically healthy dogs. APC induced cell-mediated immunological responses against melanoma cells and prolonged survival period.b) Against Babesia microti and Babesia rodhaini. Murine bone marrow-derived APC pulsed with Babesia microti infected erythrocytes induced decrease of parasitemia and increased survival rate in mice infected with Babesia rodhaini. These results suggested that APC-mediated therapy is an available manner for protozoan and cancer diseases.

对抗原提呈细胞（APC）和APC介导的免疫治疗对Th 1/Th 2细胞分化的调节机制进行了3年的研究（2004 - 2007年）获得以下结果。1）某些疾病中的Th 1/Th 2细胞分化，如鼠巴贝西虫病、犬恶性黑色素瘤和组织细胞肉瘤：a）APC（包括脾巨噬细胞）产生的IL-12 p70诱导Th 1细胞分化，并与田鼠巴氏杆菌感染中的暂时性寄生虫血症密切相关。B）建立了7株犬组织细胞肉瘤细胞系。2）Th 1/Th 2细胞分化的刺激因子：a）从感染田鼠Bababelimicroti和罗氏Babelirodhaini红细胞的培养液中分离纯化了巨噬细胞产生IL-12的刺激因子，并通过IL-12诱导Th 1细胞分化。这些因子具有热稳定性和可溶性，并且它们的洗脱曲线在东方Babelioti和罗达巴氏Babelirodhaini培养基中有很大差异。3）APC介导的免疫治疗a）针对犬恶性黑色素瘤：用犬黑色素瘤细胞系的裂解物脉冲来自骨髓的犬APC，并将其移植到临床健康犬中。APC诱导细胞介导的抗黑色素瘤细胞的免疫应答并延长存活期。B）抗田鼠巴氏杆菌和罗达巴氏杆菌。小鼠骨髓来源的APC与感染的红细胞致敏后，可降低罗带巴氏巴氏杆菌感染小鼠的寄生虫血症，提高存活率。这些结果表明，APC介导的治疗原虫和肿瘤疾病是一种可行的方式。