We hypothesize that cell mediated immunity (CMI) plays an important role in the development of experimental glomerulonephritis (GN) and GN in man. We have developed a model of experimental autoimmune glomerulonephritis (EAG) in chickens. This GN is associated with hypercellularity which is unrelated to the amount of antibody deposited, cannot be transferred with eluted antibody, occurs in humorally incompetent chickens in which no antibody is deposited, and can be transferred with specifically sensitized mononuclear cells in the absence of antibody. The hypercellularity appears to result mostly from an increase in endogenous mesangial cells with the appearance of macrophage-like cells and lymphocyte-like cells. The identity of the cells producing hypercellularity, the type of cells that transfer the disease, and the mechanism of development of GN in the absence of antibody remain to be elaborated. There are no other animal models of GN in the absence of exogenous immune reactants. The model is analogous to many types of GN in man which occur with minimal or no immune deposits.
The specific aims of the present proposal include 1) further refinement of the model utilizing thymectomy and attempts to transfer glomerular bound sensitized cells, 2) the development of monoclonal antibodies to various CMI components and glomerular constituents, 3) the development of glomerular/mesangial cell culture techniques, 4) use of the monoclonal antibodies as probes to identify cells involved in the EAG and as functionally selective agents to deplete various subsets of CMI constituents prior to transfer of cells, 5) in vitro attempts to assess the effect of cells with antigen on glomerular/mesangial cell cultures with the ultimate goal of identifying a mesangial cell growth factor. This model of CMI mediated GN is unique and pertinent to human disease. The results of these studies should provide major information regarding the role of CMI and the pathogenesis of this EAG in animals and, by extrapolation, to man. Through a better understanding of the pathogenesis of GN in animals we should hopefully be better able to prevent and treat disease processes in man and thus make inroads into that group of patients who develop end stage renal disease from similar types of GN. When one considers the personal, social and financial costs of end stage renal disease secondary to GN, the benefit of better understanding and knowledge of the pathogenesis of the disease is self evident.
