T-CELLS AND MACROPHAGES IN TRYPANOSOMA BRUCEI-RELATED GLOMERULOPATHY

In a previous study, susceptibility for Trypanosoma brucei-related glo merulopathy in mice was shown to be dependent on non-major histocompat ibility complex genes. Glomerular disease in this model could not be e xplained by the production of autoantibodies alone. In order to analyz e which part of the defense system, in addition to the B-cell compartm ent, is involved in the development of this infection-related glomerul ar disease, groups of athymic (BALB/c rnu/rnu), splenectomized, or mac rophage-depleted BALB/c mice were inoculated with T. brucei parasites. Polyclonal B-cell activation, invariably observed in infected BALB/c mice, was absent in BALB/c rnu/rnu mice. Glomerular disease in athymic mice, however, as defined by albuminuria and deposition of immune com plexes, was not different from that seen in euthymic infected BALB/c m ice. Splenectomy prior to inoculation of parasites led to a decreased incidence of albuminuria in 40% of the animals, whereas splenectomy 21 days after inoculation reduced albuminuria significantly, suggesting a role for spleen cells in the induction of glomerular disease. After macrophage depletion with liposome-encapsulated dichlorodimethylene-di phosphonate, infected BALB/c mice developed significantly higher album inuria levels for a period up to 2 weeks after depletion. Therefore, i t was concluded that the development of T. brucei-related glomerular d isease is independent of thymus-matured T cells, while the involvement of macrophages in the development of proteinuria is inhibitory rather than disease inducing. Spleen cells other than thymus-dependent T cel ls, B cells, and macrophages should be investigated for their role in the pathogenesis of this glomerulopathy.