Lupus nephritis affects large numbers of people in this country and is a major contributor to the process of chronic renal failure. Present evidence suggests the direct participation of several immunologic effector mechanism in the pathogenesis of lupus nephritis. These processes, which include selective polyclonal B cell activation, immune complex formation, and cell-mediated cytotoxicity are probably modulated by genetic constraints collaborating with humoral and cell-mediated regulatory influences which follow rules formulated in present-day network theories of immunologic science. The basic goal of this research proposal is to further characterize the pathogenesis of disease activation and immune regulation in an experimental model of lupus nephritis. These studies will closely examine the role of alloreactive T helper cells in the activation of B cells and cytotoxic effector cells. Immunoregulation by T suppressor cells will be examined and we will explore the possible role of T contrasuppressor cells and anti-idiotypic networks in the modulation of suppressive influences. Our investigations will employ a murine model of chronic graft-versus-host disease which closely approximates the clinical disorder of lupus seen in humans. We will utilize in vitro assays of cell mediated cytotoxicity, cell proliferation, and anti-DNA antibody synthesis and we will utilize antisera capable of selective recognition of subpopulations of lymphocytes. Following this acquisition of basic information, methods of manipulating these immune events will be developed so as to derive a rational basis for immunoprophylaxis or selected immunotherapy. Such studies should ultimately allow us to devise appropriate strategies for favorably altering the natural history of lupus nephritis in humans.
NIH ExPorter
NIH ExPorter