Immune reactivity and immunosuppressive intervention (TLI) in experimental nephritis. I. Immunopathologic correlates in the accelerated autologous form of nephrotoxic serum nephritis.

The progression of histologic changes observed in the accelerated autologous form of nephrotoxic serum nephritis (AA-NTSN) in the inbred LEW rat, ranging from minimal endocapillary proliferation to marked endo- and extra-capillary proliferation together with fibrin deposition and necrosis of glomerular tufts, was closely correlated (day 8) with parallel measures of albuminuria (1.6 leads to 280 mg/24 hr). In the induction phase of AA-NTSN (day 0) a direct linear correlation (r = 0.72, p less than 0.05) was obtained between anti-SGG antibody levels and 24-hr urine albumin excretion. Subsequent observations (day 7) yield an inverse correlation between anti-SGG antibody and albuminuria (r = -0.54, p less than 0.01), and this change was shown to be related to the loss of specific antibody in the urine (r = 0.59, p less than 0.025). Although splenic T cells of rats with AA-NTSN manifest a specific proliferative response to the inducing antigen SGG, and although the magnitude of this proliferative response (day 7) correlates directly with parallel measures of urine albumin excretion (r = 0.71, p less than 0.02), delayed-type hypersensitivity (DTH) to SGG measured by radiometric ear assay was inversely correlated with albuminuria in this model of experimental nephritis (r = 0.80, p less than 0.01). Additional data are presented that strongly suggest that persistent albuminuria at 1 mo after induction of AA-NTSN is independent of ongoing immunopathologic processes. Thus, glomerular injury in AA-NTSN, previously linked to prominent glomerular macrophage accumulation, is shown to be primarily dependent on a brisk antibody response to the planted heterologous (sheep) immunoglobulin, whereas cellular immunity, readily demonstrated in the splenic T cell compartment, is likely to be of lesser import in the pathogenesis of this lesion in the intact animal.