Kelly C J, Neilson E G
J Exp Med. 1987 Jan 1;165(1):107-23. doi: 10.1084/jem.165.1.107.
We have used the murine model of spontaneous autoimmune interstitial nephritis in kdkd mice to examine the importance of abnormal immunoregulation in the expression of disease. T cells from naive congenic CBA/Ca mice suppress both histologic renal injury in the kdkd strain as well as the DTH reactivity to CBA/Ca renal tubular antigens mediated by lymphocytes from nephritic kdkd mice. These antigen-specific suppressor T cells are Lyt-2+, L3T4+, I-Jk+, genetically dominant and I-Jk restricted. Unfractionated spleen cells from young, prenephritic kdkd mice also demonstrate such suppressor function. Shortly preceding disease onset, however, net suppression is functionally bypassed by emergent contrasuppressor T cells. These regulatory cells are also Lyt-2+ and I-Jk+, and adhere both to the Vicia Villosa lectin and CBA/Ca TBM. By admixing these contrasuppressor cells with spleen cells from non-disease-prone CBA/Ca mice we were able to demonstrate the presence of DTH-reactive and nephritogenic effector cells in the latter population. Such nephritogenic effector cells could also be simply demonstrated after depletion of the suppressor cells with anti-I-Jk mAbs and complement. These findings support a role for contrasuppressor cells in the abrogation of tolerance to parenchymal self-antigens.
我们利用kdkd小鼠自发性自身免疫性间质性肾炎的小鼠模型，来研究异常免疫调节在疾病表达中的重要性。来自纯合子同基因CBA/Ca小鼠的T细胞既能抑制kdkd品系小鼠的组织学肾损伤，也能抑制由患肾炎的kdkd小鼠淋巴细胞介导的对CBA/Ca肾小管抗原的迟发型超敏反应（DTH）。这些抗原特异性抑制性T细胞为Lyt-2⁺、L3T4⁺、I-Jk⁺，具有遗传显性且受I-Jk限制。来自年轻的、未患肾炎的kdkd小鼠的未分级脾细胞也表现出这种抑制功能。然而，在疾病发作前不久，新出现的抗抑制性T细胞在功能上绕过了净抑制作用。这些调节性细胞也是Lyt-2⁺和I-Jk⁺，并且既能黏附于绒毛豌豆凝集素，也能黏附于CBA/Ca肾小管基底膜（TBM）。通过将这些抗抑制性细胞与不易患疾病的CBA/Ca小鼠的脾细胞混合，我们能够证明后者群体中存在DTH反应性和致肾炎效应细胞。在用抗I-Jk单克隆抗体和补体耗尽抑制性细胞后，也能简单地证明存在这种致肾炎效应细胞。这些发现支持抗抑制性细胞在消除对实质自身抗原的耐受性中发挥作用。
