Duthie Malcolm S, Kahn Maria, Zakayan Arsen, White Maria, Kahn Stuart J
Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, WA 98104, USA.
Clin Vaccine Immunol. 2007 Aug;14(8):1005-12. doi: 10.1128/CVI.00087-07. Epub 2007 May 30.
Trypanosoma cruzi infection causes Chagas' disease, a chronic inflammatory disease. The specific inflammatory responses that cause Chagas' disease remain unclear, but data argue that parasites that persist in the host stimulate chronic self-damaging immune responses. Because T. cruzi appears to stimulate self-damaging responses, the enthusiasm to develop vaccines that boost antiparasite responses that might increase self-damaging responses has been limited. We previously demonstrated that immunization with a T. cruzi trans-sialidase protein or adoptive transfer of trans-sialidase-specific T-cell clones decreased parasitemia, morbidity, and mortality. Here we report that immunization or adoptive transfer with the protein or clones, before or during T. cruzi infection, boosts the anti-T. cruzi immune response without exacerbating acute or chronic tissue inflammation. These results argue that prophylactic and therapeutic immunotherapy for Chagas' disease can be developed safely.
克氏锥虫感染会引发恰加斯病,这是一种慢性炎症性疾病。引发恰加斯病的具体炎症反应尚不清楚,但有数据表明,宿主体内持续存在的寄生虫会刺激慢性自我损伤性免疫反应。由于克氏锥虫似乎会刺激自我损伤性反应,因此开发可能会增加自我损伤性反应的增强抗寄生虫反应疫苗的热情受到了限制。我们之前证明,用克氏锥虫转唾液酸酶蛋白进行免疫或转唾液酸酶特异性T细胞克隆的过继转移可降低寄生虫血症、发病率和死亡率。在此我们报告,在克氏锥虫感染之前或期间用该蛋白或克隆进行免疫或过继转移,可增强抗克氏锥虫免疫反应,而不会加剧急性或慢性组织炎症。这些结果表明,恰加斯病的预防性和治疗性免疫疗法可以安全地开发。