Abstracts (complete list) - Wissenschaft Online

Felix Heymann, Emma E. Hamilton-Williams, Isis Ludwig-Portugall, Susan Quaggin,
Jürgen Floege, Hermann-Josef Gröne, Christian Kurts
Immunopathology of T cell-mediated glomerulonephritis
The different forms of immune-mediated glomerulonephritis (GN) represent a major
cause of end stage kidney disease. The role of antibodies and immune-complexes has
been extensively studied, whereas the ability of T cells to mediate glomerular damage
has been proposed, but awaits experimental verification. We have generated transgenic
mice expressing a fusion protein consisting of chicken ovalbumin and hen egg lysozyme
as a model autoantigen in glomerular podocytes under the control of the nephrin
promoter (NOH mice). Injection of transgenic OVA-specific T cells into NOH mice
allowed to determine the type of renal immunopathology mediated by T cells specific for
a glomerular autoantigen. OVA-specific CD8+ effector T cells (OT-I cells) were activated
by cross-presentation and proliferated in the renal lymph nodes of NOH mice. Injection
of activated OT-I cells increased cross-presentation in this node, presumably by
cytotoxic release of antigen from the kidney. Renal immunopathology was only
observed when with OT-I cells were co-injected with activated OVA-specific CD4+
helper cells (OT-II cells). Surprisingly, the typical form of podocyte damage, namely
foot process fusion, was not detected. Instead, immunopathology was dominated by
periglomerular mononuclear infiltration, reminiscent of transplant glomerulitis or of
rapid progressive forms of glomerulonephritis. Adjacent to this infiltrate, the parietal
glomerular epithelial cells showed signs of injury. Repetitive injection of OT cells
resulted in proteinuria, reduced creatinin-clearance and structural kidney damage
accompagnied by massive periglomerular infiltartes. These infiltrates contained many
dendritic cells expressing CD11c, CD11b, F4/80, and CD8, which showed signs of
activation. Ablation of these DC resolved the inflammatory infiltrate, demonstrating a
functional role of kidney DC in mediating kidney damage. In conclusion, we
demonstrate that T cells can recruit kidney DCs to induce periglomerular infiltrates
resulting in glomerular immunopathology.