Prevention of nephritis in major histocompatibility complex class II-deficient MRL-lpr mice.
MRL-lpr mice develop aggressive autoimmune kidney disease associated with increased or de novo renal expression of major histocompatibility complex (MHC) class II molecules and a massive systemic expansion of CD4-CD- double negative (DN) T cells. Whereas non-MHC linked genes can have a profound effect on the development of nephritis, lymphadenopathy, and anti-DNA antibody production in MRL-lpr mice, the role of MHC molecules has not been unequivocally established. To study the role of MHC class II in this murine model of systemic lupus erythematosis, class II-deficient MRL-lpr mice (MRL-lpr -/-) were created. MRL-lpr -/- mice developed lymphadenopathy but not autoimmune renal disease or autoantibodies. This study demonstrates that class II expression is critical for the development of autoaggressive CD4+ T cells involved in autoimmune nephritis and clearly dissociates DN T cell expansion from autoimmune disease initiation.
Jevnikar
A M
AM
Robarts Research Institute, University of Western Ontario, London, Canada.
Grusby
M J
MJ
Glimcher
L H
LH
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D009393:Nephritis / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II