Li Haiyan S, Ligons Davinna L, Rose Noel R, Guler Mehmet L
Department of Pathology, The John Hopkins University, Baltimore, MD 21205, USA.
J Immunol. 2008 Jun 1;180(11):7480-4. doi: 10.4049/jimmunol.180.11.7480.
Bone marrow (BM) transplantation has been used to study the cellular basis of genetic control of autoimmune diseases, but conclusions remain elusive due to the contradictory findings in different animal models. In the current study, we found that BM cells from myocarditis-susceptible A.SW mice can render irradiated, myocarditis-resistant B10.S recipient mice susceptible to myosin-induced myocarditis, indicating that hematopoietic cells express the genetic differences controlling susceptibility to autoimmune myocarditis. We then sought to differentiate the role of lymphoid vs nonlymphoid components of BM in the pathogenesis of myocarditis by comparing mixed chimeras receiving BM from A.SW wild-type or RAG(-/-) mice mixed with BM from B10.S wild-type mice. This experiment clearly demonstrated that T and B lymphocytes were indispensable for transferring the susceptible phenotype to disease-resistant recipients. Our findings significantly narrow the cellular expression of genetic polymorphisms controlling the EAM phenotype.
骨髓（BM）移植已被用于研究自身免疫性疾病遗传控制的细胞基础，但由于不同动物模型中的矛盾发现，结论仍然难以捉摸。在当前研究中，我们发现来自易患心肌炎的A.SW小鼠的骨髓细胞可使经辐射、抗心肌炎的B10.S受体小鼠易患肌球蛋白诱导的心肌炎，这表明造血细胞表达了控制自身免疫性心肌炎易感性的遗传差异。然后，我们试图通过比较接受来自A.SW野生型或RAG（-/-）小鼠的骨髓与来自B10.S野生型小鼠的骨髓混合的混合嵌合体，来区分骨髓中淋巴细胞与非淋巴细胞成分在心肌炎发病机制中的作用。该实验清楚地表明，T和B淋巴细胞对于将易感表型传递给抗病受体是不可或缺的。我们的发现显著缩小了控制实验性自身免疫性心肌炎（EAM）表型的遗传多态性的细胞表达范围。
