LUPUS NEPHRITIS IN THE ABSENCE OF RENAL MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II MOLECULES

MRL/Mp-lpr/lpr (MRL-lpr) mice develop an aggressive autoimmune disorde r characterized by arthritis, vasculitis, and glomerulonephritis. Rena l injury is associated with increased expression of major histocompati bility complex (MHC) molecules, as well as cytokines, adhesion molecul es (intracellular adhesion molecule-1, vascular cell adhesion molecule -1), and autoantibodies. By using either MHC Class I (MRL-lpr B2m(-/-) ) or MHC Class II deficient (MRL-lpr Ab(-/-)) kidneys in a transplant model, we tested the role of renal expression of these molecules in th e development of autoimmune renal injury. Kidneys from MRL-lpr B2m(-/- ) or MRL-lpr Ab(-/-) mice as well as control wild-type mice transplant ed into MRL-lpr wt/- recipients developed nephritis, CD4+ and CD8+ T c ell infiltration, and heavy glomerular deposition of immunoglobulin. S pontaneously proliferating autoreactive T cells were found in wild-typ e MRL-lpr and MRL-lpr B2m(-/-) but not MRL-lpr Ab(-/-) mice. These res ults suggest that the absence of renal expression of either Class I or Class II molecules does not provide marked protection from autoimmune lupus nephritis and supports the possibility that protection from aut oimmune disease in MRL-lpr Ab(-/-) mice is related to the loss of auto reactive MHC Class II-dependent CD4+ T cells.