抗GBM肾小球肾炎发病机制研究进展.ppt

The importance of cell-mediated immunity in the course and severity of autoimmune anti-glomerular basement membrane disease in mice Glomerular changes 11 wk and 6 months after Immunization with r-α3(IV)NC1. A) GBM ruptures, B) glomerular crescents, and C) glomerular sclerosis were counted in PAS-stained kidney sections at 11 wk and 6 months after the initial immunization. Although there is no difference in the number of A) glomeruli with GBM ruptures between DBA/1 and C57BL/6 mice at 11 wk, there is a significant difference in the number of B) crescents formed and C) sclerotic glomeruli. C57BL/6 and AKR have developed a similar number of crescents and sclerotic glomeruli 6 months postimmunization. IgG-staining of the GBM was scored at 11 wk and 6 months (C). There are significant differences in the number of glomeruli stained strongly at 11 wk. Again, the results obtained for C57BL/6 and AKR at 6 months are similar to the DBA/1 data at 11 wk. Results represent the mean ± of each group. *P 0.05, **P 0.005. Anti-glomerular basement membrane (GBM) disease is a rapidly progressive glomerulonephritis (GN) resulting from autoimmunity against the Goodpasture antigen α3(IV)NC1. In addition to the well-characterized antibody contribution, a T helper 1 (Th1) response has been suspected as the culprit for glomerular injury. We induced anti-GBM disease in DBA/1, C57BL/6, AKR, and NOD mice with recombinant human α3(IV)NC1 to investigate the involvement of humoral and cellular autoimmunity. DBA/1 mice had crescentic GN 11 wk postimmunization with α3(IV)NC1. C57BL/6 and AKR mice developed a chronic disease course resulting in comparable kidney injury to DBA/1 mice within 6 months. NOD revealed only minor glomerular changes. The rapid course and the severity of the disease in DBA/1 mice can be explained by our immunological findings in their sera and splenocytes: 1) high antibody titers specific for the putative clinically relevant epitope of α3(IV)NC1 with Th1-type isotypes,