The liver of MRL/lpr mice contains defective accessory cells and a population of immunosuppressive lymphocytes.
Immunoregulatory abnormalities in the MRL/lpr mouse strain include activation of macrophages and hepatic natural killer cells, spontaneous production of tumor necrosis factor, defective oral tolerance, and impaired production of interleukin-2. Because the liver is the major organ responsible for the clearance, degradation, and presentation of foreign antigens from the gastrointestinal tract, we have investigated antigen presentation activity of hepatic nonparenchymal cells (NPC) from MRL/lpr, MRL/++, and C3H/HeN female mice in the primary immune response as measured by stimulation of allogeneic one-way mixed lymphocyte response (MLR), and allogeneic cell-mediated lympholysis (CML). Whereas adherent NPC from C3H/HeN, MRL/++, and young MRL/lpr mice were effective stimulators, NPC from MRL/lpr mice older than 9 weeks were defective stimulators of both MLR and CML responses. This abnormality was not observed in splenic accessory cells from these mice. Moreover, a population of hepatic NPC from older MRL/lpr mice are immunosuppressive: mixing of MRL/lpr NPC with splenic stimulators from MRL/++ mice profoundly inhibited primary allogeneic CML responses. The inhibitory hepatic nonparenchymal cell population was nonadherent, radioresistant and was removed by pretreatment with antibodies to either asialoAGM-1 or Lyt-2 plus complement. This inhibition was not observed with the addition of MRL/++ NPC or supernates from cultured MRL/lpr NPC. These findings suggest a selective organ-specific and age-dependent impairment of antigen presentation and the presence of an immunosuppressive lymphocyte population in the liver of MRL/lpr mice which may contribute to the autoimmune process.
Magilavy
D B
DB
Department of Pediatrics, La Rabida-University of Chicago Institute, Illinois 60649.
Rowley
D A
DA
Davis
M
M
D000367:Age Factors; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D008099:Liver / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*