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 disorder characterized by arthritis, vasculitis, and glomerulonephritis. Renal injury is associated with increased expression of major histocompatibility complex (MHC) molecules, as well as cytokines, adhesion molecules (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 the development of autoimmune renal injury. Kidneys from MRL-lpr B2m-/- or MRL-lpr Ab-/- mice as well as control wild-type mice transplanted into MRL-lpr wt/- recipients developed nephritis, CD4+ and CD8+ T cell infiltration, and heavy glomerular deposition of immunoglobulin. Spontaneously proliferating autoreactive T cells were found in wild-type MRL-lpr and MRL-lpr B2m-/- but not MRL-lpr Ab-/- mice. These results 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 autoimmune disease in MRL-lpr Ab-1- mice is related to the loss of autoreactive MHC Class II-dependent CD4+ T cells.
Mukherjee
R
R
Robarts Research Institute, London, Ontario, Canada.
Zhang
Z
Z
Zhong
R
R
Yin
Z Q
ZQ
Roopenian
D C
DC
Jevnikar
A M
AM
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D000974:Antibodies, Antinuclear / Q000032:analysis; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012313:RNA