Figure 7.

MHC II expressed on podocytes is essential for the induction of severe anti-GBM nephritis. Transgenic mice expressing the Cre recombinase exclusively in podocytes were crossed in a mouse line expressing a floxed MHC class II gene. In the F3 offspring and control littermates, an anti-GBM nephritis was induced as described in Figure 6. The kidneys were analyzed by histology and FACS. Exemplified periodic acid–Schiff staining is shown from mice without MHC class II (A and C) on podocytes and (B and D) from control animals. The quantification of three independent experiments is shown in E (percent crescentic glomeruli) and F (glomerulosclerosis index). The FACS gating strategy is shown in G–I. (J–L) The quantifications are shown as box plots (box-and-whisker diagrams graphically depicting the lowest number observed, lower quartile, median, upper quartile, and largest observation). **P<0.001. (G and J) First, the relative frequencies of CD45+ leukocytes in the kidneys were calculated; (H and I) subsequently, the main subpopulations of the leukocytes were analyzed, and within the CD45/CD4 double-positive populations, the frequencies of effector memory cells (CD44 high/CD62L low) were determined. Please note that most control animals displayed serve glomerulosclerosis, pronounced and frequent crescent formation, and infiltration of CD4+ effector memory cells. This result was not seen in mice lacking MHC class II expression selectively on podocytes.