The role of T cells in the mediation of glomerular injury in Heymann's nephritis in the rat

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Abstract
Heymann's nephritis (HN), a rat model of the membranous glomerulonephritis In man, is thought to be mediated by auto-lg with subsequent activation of C. Whether T cell mechanisms are Involved in the mediation of HN, apart from CD4+ cells providing help for auto-lg production, was examined by treatment with mAb specific for T cell subsets for 6 weeks after Immunization to Induce HN. Anti-CD4 mAb therapy totally prevented proteinuria, in that at 6, 8, and 12 week treated rats had 260 mg/day. Ig and C deposition In the glomerulus was significantly less and auto-lg tlters In serum were partially suppressed by antl-CD4 therapy. Anti-CD8 mAb therapy markedly reduced proteinuria at all time points, for example at 6 weeks there was 51 ± 40 mg/day compared to 183 ± 120 mg/day (P = 0.0003), but had no effect on auto-lg titers or on Ig and C deposition in the glomerulus. A non-specific effect of high dose mouse mAb therapy was excluded by the findings that a mAb that did not bind to rat cells had no effect on the Induction of HN and that serum C was not depleted in any of the mAb treated animals. A role for T effector mechanisms was further supported by the finding that therapy with mAb to T cell receptor α/β chain or with cyclosporlne also markedly delayed the onset of proteinuria. Examination of renal biopsies showed a T cell infiltrate in glomeruli and the interstitium of the untreated HN controls that was not present in MRC 0x35 or MRC 0x8 treated groups. This Infiltrate included CD4+ and CD8+ T cells and macrophages. These results suggest induction of proteinuria in HN was totally dependent upon CD4+ T cells, and that CD4+ and CD8+ cells may have a direct role in the mediation of glomerular dysfunction In HN.

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