CD4+ T cells recognizing specific antigen deposited in glomeruli cause glomerulonephritis-like kidney injury.
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-gamma 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.
Radeke
Heinfried H
HH
Pharmazentrum Frankfurt, Clinic of the Goethe University, Frankfurt-am-Main, Germany. radeke@em.uni-frankfurt.de
Tschernig
Thomas
T
Karulin
Alexey
A
Schumm
Georg
G
Emancipator
Steve N
SN
Resch
Klaus
K
Tary-Lehmann
Magdalena
M
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology; D005921:Glomerulonephritis / Q000276:immunology* / Q000652:urine; D007156:Immunologic Memory; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010047:Ovalbumin; D011507:Proteinuria; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors
D000941:Antigens; D010047:Ovalbumin