CD4 + T Cells Recognizing Specific Antigen Deposited in Glomeruli Cause Glomerulonephritis-like Kidney Injury

Abstract

To investigate, whether T lymphocytes alone are sufficient to induce glomerulonephritis, a model in SCID mice was developed. Conditions for the generation and exclusive glomerular targeting of crosslinked ovalbumin (OVA) polymers and a series of OVA-specific T-cell clones and lines were established. Only a well-defined subfraction of OVA polymers exclusively targeted to the glomerular mesangium without causing local alteration in the absence of IgG. From numerous T-cell preparations spanning different Th-1/-2 profiles one T-helper cell clone characterized by ELISPOT assay as pure Th-1 (IFN-γ and IL-2) induced nephritislike pathology. Histological examination at days 1, 2, 5, and 21 showed major infiltrates in proximal tubular regions (PTR) at day 5 accompanied by significant proteinuria. No injury was observed after deposition of irrelevant antigen or injection of other T-cell preparations. Detailed histological analysis revealed that Th-1 cell numbers peaked early in glomeruli (2.1 ± 0.6 vs 0/gcs). Macrophages, however, were hardly detectable in glomeruli (0.5 ± 0.3/gcs) at this time, while they formed the major constituent of the PTR infiltrates at day 5 (83 ± 1). These data in a new SCID nephritis model indicate that memory Th-1 cells together with localized antigen presenting cells trigger nephritis.