Heeger P S, Smoyer W E, Jones M, Hopfer S, Neilson E G
Department of Medicine, Cleveland VA Medical Center, Ohio, USA.
Kidney Int. 1996 May;49(5):1222-30. doi: 10.1038/ki.1996.176.
Anti-tubular basement membrane disease (alpha TBM) produces T cell-mediated interstitial nephritis in SJL/J mice following immunization with heterologous renal tubular antigen. Initial mononuclear infiltrates appear in vivo after six to eight weeks, with subsequent progression to renal fibrosis and endstage kidney disease. Cultured lymph node derived nephritogenic T cells from these mice react to a small epitopic region of the 3M-1 target antigen and share a common amino acid motif in their V beta CDR3 regions. We now have used RT-PCR to further characterize the renal expression of T cell receptor (TcR) V beta gene repertoires during the course of this disease. Individual kidneys with focal mononuclear infiltrates characteristic of early alpha TBM disease express up to three different TcR V beta genes; however, the same V beta genes are not found in all kidneys at the same early stage of injury. DNA sequencing of the V beta RT-PCR products reveals a heterogeneous population of VDJ recombinations and deduced CDR3 amino acid sequences. Our studies do not support TcR V beta region gene restriction in histologically-detectable alpha TBM disease, but are more consistent with a dynamic, organ-specific autoimmune disease, directed at multiple autoantigenic epitopes.
抗肾小管基底膜病（αTBM）在用异源肾小管抗原免疫后的SJL/J小鼠中产生T细胞介导的间质性肾炎。最初的单核细胞浸润在六到八周后出现在体内，随后进展为肾纤维化和终末期肾病。从这些小鼠培养的淋巴结源性致肾炎T细胞对3M-1靶抗原的一个小表位区域产生反应，并且在其VβCDR3区域共享一个共同的氨基酸基序。我们现在使用逆转录聚合酶链反应（RT-PCR）来进一步表征这种疾病过程中T细胞受体（TcR）Vβ基因库的肾脏表达。具有早期αTBM疾病特征性局灶性单核细胞浸润的单个肾脏表达多达三种不同的TcR Vβ基因；然而，在损伤的同一早期阶段，并非所有肾脏都能发现相同的Vβ基因。Vβ RT-PCR产物的DNA测序揭示了VDJ重组的异质群体和推导的CDR3氨基酸序列。我们的研究不支持在组织学可检测的αTBM疾病中TcR Vβ区域基因受限，而是更符合一种针对多个自身抗原表位的动态、器官特异性自身免疫性疾病。
