Journal
CLINICAL IMMUNOLOGY
Volume 104, Issue 2, Pages 161-173Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/clim.2002.5246
Keywords
SCID; nephritis; T lymphocytes; dendritic cells; ELISPOT assay; immunospot; antigen presentation; inflammation; mesangial
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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 nephritis-like 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. (C) 2002 Elsevier Science (USA).
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