T Cell-mediated Induction of Anti-GBM Glomerulonephritis in WKY Rats

Glomerulonephritis induced in Wistar Kyoto (WKY) rats by the intravenous administration of rabbit anti-glomerular basement membrane antibody is characterized by a glomerular accumulation of T lymphocytes and monocytes/macrophages, crescent formation, and massive proteinuria. Although this model was initiated by the antibody injection, the involvement of cell-mediated immunity was also suggested since a crucial role of CD8-positive T lymphocytes was demonstrated in the induction of this model. An implication of humoral and cell-mediated immunity in this model was examined in the present study. The glomerular lesions and urinary protein excretion were deteriorated in rats preimmunized with rabbit IgG or inoculated with rabbit IgG-sensitized rat lymphocytes before the glomerular basement membrane (anti-GBM) antibody administration. In contrast, the anti-GBM glomerulonephritis was ameliorated by the passive transfer of a rat anti-rabbit IgG antibody. These observations suggested that cell-mediated immunity advanced the disease and humoral immunity suppressed it. We then examined the involvement of T cell receptor αβ on T lymphocytes by administrating a monoclonal antibody against the receptor (R73) in rats before or after the anti-GBM antibody injection. Pretreatment with the antibody markedly suppressed the glomerular lesion and proteinuria. However, the suppressive effect was minimal in rats given the antibody after the anti-GBM antibody injection. These results showed that the anti-GBM nephritis in WKY rats was mediated by T cell receptor αβ to initiate cell-mediated immunity.