Agersborg S S, Garza K M, Tung K S
Department of Microbiology, University of Virginia, Charlottesville 22908, USA.
Eur J Immunol. 2001 Mar;31(3):851-9. doi: 10.1002/1521-4141(200103)31:3<851::aid-immu851>3.0.co;2-9.
Genetic and environmental factors both influence autoimmune disease occurrence, but the identity and mechanism of action of environmental factors are poorly understood. Here we show that pinworm-infected neonatal but not adult mice, injected with an ovarian self peptide of the zona pellucida protein 3 (pZP3) in water and without adjuvant, develop Th2 responses and severe eosinophilic autoimmune ovarian disease. A strong Th2 memory response is recalled when, as adults, the mice are challenged with a regimen that elicits a strong Th1 response in naive adults. The strong Th2 autoimmune response included high levels of IL-4 and IL-5 production by pZP3-specific T cells, and an IgG1-biased autoantibody response. The Th2 response ended promptly upon pinworm eradication, and partially resurfaced upon re-infection. We conclude that the rodent pinworm is an environmental agent that modifies the neonatal response to a self peptide, resulting in termination of the tolerance state and induction of a strong Th2-associated autoimmune disease and T cell memory.
遗传和环境因素都会影响自身免疫性疾病的发生，但环境因素的特性和作用机制仍知之甚少。在此我们表明，感染蛲虫的新生小鼠而非成年小鼠，在无佐剂的情况下经水注射透明带蛋白3（pZP3）的卵巢自身肽后，会产生Th2反应并引发严重的嗜酸性自身免疫性卵巢疾病。当这些小鼠成年后，用能在未接触过抗原的成年小鼠中引发强烈Th1反应的方案进行攻击时，会唤起强烈的Th2记忆反应。强烈的Th2自身免疫反应包括pZP3特异性T细胞产生高水平的IL-4和IL-5，以及以IgG1为主的自身抗体反应。蛲虫根除后，Th2反应迅速终止，再次感染时会部分重现。我们得出结论，啮齿动物蛲虫是一种环境因子，它会改变新生小鼠对自身肽的反应，导致耐受状态终止，并引发强烈的Th2相关自身免疫性疾病和T细胞记忆。
