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用负载PIII的培养巨噬细胞免疫的小鼠中,对曼氏血吸虫卵的肉芽肿超敏反应的调节。

Modulation of granulomatous hypersensitivity against Schistosoma mansoni eggs in mice vaccinated with culture-derived macrophages loaded with PIII.

作者信息

Gustavson Shauma, Zouain Cláudia S, Alves José Bento, Leite M Fatima, Goes Alfredo M

机构信息

Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), MG, Belo Horizonte, Brazil.

出版信息

Parasitol Int. 2002 Sep;51(3):259-69. doi: 10.1016/s1383-5769(02)00031-4.

Abstract

Granuloma modulation induced by antigen is an attractive model for vaccination studies of experimental schistosomiasis to test the effect of anti-pathology vaccine. We describe here an immunization procedure with culture derived macrophages-pulsed PIII, a known anionic antigen purified from S. mansoni adult worm, involved in the inhibition of granulomatous response to eggs. For our studies, peritoneal or spleen macrophages cultured over 15 days were loaded with PIII. Both macrophage sub-populations were capable to efficiently take up and subsequently present PIII to lymphocytes as evidenced by immunofluorescence assay. The vaccination of mice with intravenous injection of PIII-loaded macrophages potently induced antigen-specific immune response to S. mansoni antigens as determined by cell proliferation assay. This immunization procedure of mice caused significant decrease in hepatic granuloma formation and in vitro granuloma reaction to S. mansoni antigens coupled to polyacrylamide beads (PB-SEA, PB-SWAP or PB-PIII). Assessment of in vitro granuloma supernatant of spleen cells from PIII-loaded macrophages vaccinated mice revealed significant amounts of Th1-cytokines IFN-gamma and IL-2 compared to control cells. Collectively, our results indicate that culture derived-macrophages provided a valuable research tool to investigate aspects of immune response that promote modulation of granulomatous hypersensitivity to S. mansoni eggs in mice.

摘要

抗原诱导的肉芽肿调节是实验性血吸虫病疫苗接种研究中用于测试抗病理疫苗效果的一个有吸引力的模型。我们在此描述一种免疫程序,即使用从曼氏血吸虫成虫中纯化的已知阴离子抗原PIII脉冲处理培养的巨噬细胞,该抗原参与抑制对虫卵的肉芽肿反应。在我们的研究中,将培养超过15天的腹膜或脾脏巨噬细胞用PIII负载。免疫荧光分析表明,这两种巨噬细胞亚群都能够有效地摄取并随后将PIII呈递给淋巴细胞。通过细胞增殖试验确定,静脉注射负载PIII的巨噬细胞对小鼠进行疫苗接种可有效诱导针对曼氏血吸虫抗原的抗原特异性免疫反应。对小鼠的这种免疫程序导致肝肉芽肿形成以及对与聚丙烯酰胺珠偶联的曼氏血吸虫抗原(PB-SEA、PB-SWAP或PB-PIII)的体外肉芽肿反应显著降低。与对照细胞相比,对负载PIII的巨噬细胞接种疫苗的小鼠脾脏细胞的体外肉芽肿上清液评估显示,Th1细胞因子IFN-γ和IL-2的含量显著增加。总体而言,我们的结果表明,培养的巨噬细胞为研究促进小鼠对曼氏血吸虫虫卵肉芽肿超敏反应调节的免疫反应方面提供了一个有价值的研究工具。

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