CD4⁺ T cells specific to a glomerular basement membrane antigen mediate glomerulonephritis

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Abstract

Ab-mediated mechanisms have been considered the major causes of glomerulonephritis (GN). However, recent studies suggest that T cells may be more important in mediating GN. To investigate the effects of antigen-specific CD4+ T cells, we generated Th1 cell lines specific for this antigen from rats that had been immunized with a recombinant form of the glomerular basement membrane (GBM) antigen, Col4α3NC1. Upon the transfer of in vitro–activated T cell lines to pertussis toxin-primed, naive syngeneic rats, the recipients developed severe proteinuria/albuminuria, which plateaued after ∼35 days. Although no IgG binding to GBM or C3 deposition could be detected by immunofluorescence, five out of eleven rats exhibited severe GN, as judged by the formation of characteristic crescent-shaped lesions in the glomerluli, whereas the others exhibited modest GN. Thus Col4α3NC1-specific T cells directly initiated glomerular injury in the recipients. One notable difference from GN induced by active immunization was a T cell infiltration in the renal interstitium, which affected some tubules. We therefore injected fluorescence-labeled Col4α3NC1-specific into naive rats, and we found that they were enriched 4.5-fold in the kidney cortex relative to nonspecific control T cells 24 hours later. Many of the T cells were located in the Bowman’s space and had a flattened shape, suggesting that the primary target for the T cells was in or adjacent to the Bowman’s capsule.

Authors

Jean Wu, John Hicks, Jason Borillo, William F. Glass II, Ya-Huan Lou