Zaccone Paola, Fehérvári Zoltán, Jones Frances M, Sidobre Stéphane, Kronenberg Mitchell, Dunne David W, Cooke Anne
Immunology Division, Department of Pathology, University of Cambridge, Cambridge, GB.
Eur J Immunol. 2003 May;33(5):1439-49. doi: 10.1002/eji.200323910.
Infection with Schistosoma mansoni (S. mansoni) or exposure to eggs from this helminth inhibits the development of type 1 diabetes in NOD mice. In this study we show that soluble extracts of S. mansoni worm or egg completely prevent onset of type 1 diabetes in these mice but only if injection is started at 4 weeks of age. T cells from diabetes-protected mice make IL-10 in recall responses to parasite antigens. These cells are furthermore impaired in their ability to transfer diabetes to NOD-SCID recipients. Bone marrow dendritic cells derived from NOD mice are found to make more IL-10 and less IL-12 following culture with S. mansoni soluble egg antigens in conjunction with lipopolysaccharides. NOD mice are deficient in NKT cells. Soluble worm and egg antigens increase the numbers of V alpha 14i NKT cells in NOD mice. These effects of schistosome antigens on the innate immune system provide a mechanism for their ability to prevent type 1 diabetes in NOD mice.
感染曼氏血吸虫(S. mansoni)或接触这种蠕虫的虫卵可抑制非肥胖糖尿病(NOD)小鼠1型糖尿病的发展。在本研究中,我们发现曼氏血吸虫虫体或虫卵的可溶性提取物能完全预防这些小鼠1型糖尿病的发病,但前提是在4周龄时开始注射。来自糖尿病受保护小鼠的T细胞在对寄生虫抗原的回忆反应中产生白细胞介素-10(IL-10)。此外,这些细胞将糖尿病转移给NOD-SCID受体的能力受损。研究发现,用曼氏血吸虫可溶性虫卵抗原与脂多糖共同培养后,源自NOD小鼠的骨髓树突状细胞产生更多的IL-10和更少的IL-12。NOD小鼠缺乏自然杀伤T细胞(NKT细胞)。可溶性虫体和虫卵抗原可增加NOD小鼠中Vα14i NKT细胞的数量。血吸虫抗原对先天免疫系统的这些作用为它们预防NOD小鼠1型糖尿病的能力提供了一种机制。