Maternal Autoantibody Triggers De Novo T Cell-Mediated Neonatal Autoimmune Disease1
Maternal Autoantibody Triggers De Novo T Cell-Mediated Neonatal Autoimmune Disease1
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DOI：
10.4049/jimmunol.170.9.4656
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发表时间：
2003-05
期刊：
影响因子：
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通讯作者：
Y. Setiady;E. Samy;K. Tung
中科院分区：
文献类型：
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作者：
Y. Setiady;E. Samy;K. Tung
虽然人类母体自身抗体可将自身免疫性疾病的短暂表现传递给其后代，但一些新生儿自身免疫性疾病可进展，导致组织结构和功能的丧失。在这项研究中，我们的文件，小鼠母体自身抗体传递给后代可以触发新生儿致病性自身反应性T细胞反应和T细胞介导的器官特异性自身免疫性疾病。透明质酸3（ZP 3）表位的自身抗体被发现诱导自身免疫性卵巢疾病（AOD）和卵巢早衰的新生儿，但不是成年小鼠。新生儿AOD没有发生在T细胞缺陷的幼崽，和卵巢病理转移的CD 4 + T细胞从患病的捐助者。有趣的是，新生儿AOD仅发生在新生儿第1-5天暴露于ZP 3自身抗体的幼崽中，而不是第7天或第9天。疾病易感性新生儿时间窗与新生儿卵巢自身免疫性炎症的倾向无关，并且不受功能性成人CD 4 + CD 25 + T细胞输注的影响。然而，在9日龄小鼠中对新生儿AOD的抗性通过CD 4 + CD 25 + T细胞耗竭而消除。最后，新生儿AOD被抗体阻断IgG-FcR，有趣的是，该疾病不是由自身抗体引起的第二个，独立的天然ZP 3 B细胞表位。因此，新生儿自身免疫的一种新机制，其中表位特异性自身抗体刺激从头自身免疫致病性CD 4 + T细胞反应。
Although human maternal autoantibodies may transfer transient manifestation of autoimmune disease to their progeny, some neonatal autoimmune diseases can progress, leading to the loss of tissue structure and function. In this study we document that murine maternal autoantibody transmitted to progeny can trigger de novo neonatal pathogenic autoreactive T cell response and T cell-mediated organ-specific autoimmune disease. Autoantibody to a zona pellucida 3 (ZP3) epitope was found to induce autoimmune ovarian disease (AOD) and premature ovarian failure in neonatal, but not adult, mice. Neonatal AOD did not occur in T cell-deficient pups, and the ovarian pathology was transferable by CD4+ T cells from diseased donors. Interestingly, neonatal AOD occurred only in pups exposed to ZP3 autoantibody from neonatal days 1–5, but not from day 7 or day 9. The disease susceptibility neonatal time window was not related to a propensity of neonatal ovaries to autoimmune inflammation, and it was not affected by infusion of functional adult CD4+CD25+ T cells. However, resistance to neonatal AOD in 9-day-old mice was abrogated by CD4+CD25+ T cell depletion. Finally, neonatal AOD was blocked by Ab to IgG-FcR, and interestingly, the disease was not elicited by autoantibody to a second, independent native ZP3 B cell epitope. Therefore, a new mechanism of neonatal autoimmunity is presented in which epitope-specific autoantibody stimulates de novo autoimmune pathogenic CD4+ T cell response.