Role of T cell subsets in anti-glomerular basement membrane glomerulonephritis

抗Goodpasture抗原α 3 IV-NC 1的自身免疫是抗肾小球基底膜（GBM）肾小球肾炎的原因。标志性特征是自身抗体沿着GBM沉积。临床和实验数据也表明T细胞在疾病发病机制中的作用。用α 3 IV-NC 1免疫DBA/1小鼠引起肾小球肾炎，其特征与人抗GBM疾病相似。在我们的项目中，我们结合联合收割机这种实验性自身免疫性肾小球肾炎（EAG）模型与高灵敏度的技术分析小T细胞群体。到目前为止，我们的研究结果显示，EAG肾脏中Th 1，Th 17和调节性T细胞，包括α 3 IV-NC 1特异性T细胞群的积累。然而，不同T细胞亚群在疾病进展中的作用尚不清楚。该项目将重点关注α 3 IV-NC 1特异性T细胞。将使用特异性免疫以及T细胞转移方法来确定α 3 IV-NC 1特异性T细胞应答在EAG发生和进展中的作用。为了解决Th 1、Th 17和调节性T细胞的一般影响，将IL-17 A、IL-23 p19或IFNγR缺陷的小鼠以及调节性T细胞可以特异性耗尽的小鼠与DBA/1背景进行回交，现在可用于EAG模型中的分析。总之，我们的研究结果将有助于阐明T细胞在实验和人类自身免疫性GN中的功能。

Autoimmunity against the Goodpasture antigen α3IV-NC1 is the cause of anti-glomerular basement membrane (GBM) glomerulonephritis. Hallmark features are the deposition of autoantibodies along the GBM. Clinical and experimental data also suggest a role for T cells in pathogenesis of disease. Immunization of DBA/1 mice with α3IV-NC1 causes glomerulonephritis with features similar to human anti-GBM disease. In our project, we combine this experimental autoimmune glomerulonephritis (EAG) model with highly sensitive techniques for the analysis of small T cell populations. Our results so far show accumulation of Th1, Th17 and regulatory T cells, including an α3IV-NC1-specific T cell population, in EAG kidneys. However, the role of the different T cell subsets in disease progression is unclear. The project will focus on α3IV-NC1 specific T cells. Specific immunization as well as T cell transfer approaches will be used to determine the role of α3IV-NC1-specific T cell responses in development and progression of EAG. To address the general impact of Th1, Th17 and regulatory T cells, mice deficient in IL-17A, IL-23p19 or IFNγR as well as mice in which regulatory T cells can be specifically depleted were backcrossed onto the DBA/1 background and are now available for analyses in the EAG model. In summary, our results will help to clarify the function of T cells in experimental and human autoimmune GN.