Smoyer W E, Kelly C J
Department of Pediatrics, University of Michigan Medical Center.
Int Rev Immunol. 1994;11(3):245-51. doi: 10.3109/08830189409061730.
kdkd mice, a mutant subline of CBA/Ca mice, develop a progressive, T cell-mediated, autoimmune interstitial nephritis which leads to renal failure and death of all mice at 20-28 weeks of age. This disease is inherited in an autosomal recessive manner, with complete penetrance, and has been linked to grizzled and waltzer on mouse chromosome 10. Immunologic evaluation of this lesion has demonstrated that histologic disease is initiated by a population of CD8+, H-2Kk-restricted T cells, which recognize an antigen in collagenase-solubilized syngeneic renal tubules. These nephritogenic effector cells can also be demonstrated in non-disease prone CBA/Ca mice. Susceptibility to autoimmune nephritis correlates with distinct expression of regulatory, rather than effector, T cells. Interstitial nephritis in kdkd mice can be inhibited by protein-calorie restriction, infusions of CBA/Ca CD8+ T cells, or monoclonal antibodies of ICAM-1. This murine model most closely resembles medullary cystic disease in humans, which has not historically been considered an autoimmune disease. Mapping of the genes for both medullary cystic disease and the defect in kdkd mice should augment our understanding of mechanisms of organ-specific autoimmunity.
kdkd小鼠是CBA/Ca小鼠的一个突变亚系，会发展出一种进行性的、T细胞介导的自身免疫性间质性肾炎，导致所有小鼠在20至28周龄时肾衰竭并死亡。这种疾病以常染色体隐性方式遗传，具有完全的外显率，并且与小鼠10号染色体上的灰化和华尔兹基因相关。对该病变的免疫学评估表明，组织学疾病由一群CD8+、H-2Kk限制性T细胞引发，这些T细胞识别胶原酶溶解的同基因肾小管中的一种抗原。这些致肾炎效应细胞在非疾病易感的CBA/Ca小鼠中也能被检测到。自身免疫性肾炎的易感性与调节性T细胞而非效应性T细胞的独特表达相关。kdkd小鼠的间质性肾炎可通过蛋白质-热量限制、注入CBA/Ca CD8+ T细胞或ICAM-1单克隆抗体来抑制。这种小鼠模型与人类的髓质囊性疾病最为相似，而髓质囊性疾病在历史上一直未被视为自身免疫性疾病。对髓质囊性疾病和kdkd小鼠缺陷的基因定位应能增进我们对器官特异性自身免疫机制的理解。
