title: Contrasuppression in autoimmunity. Abnormal contrasuppression facilitates expression of nephritogenic effector T cells and interstitial nephritis in kdkd mice.
abstract: We have used the murine model of spontaneous autoimmune interstitial nephritis in kdkd mice to examine the importance of abnormal immunoregulation in the expression of disease. T cells from naive congenic CBA/Ca mice suppress both histologic renal injury in the kdkd strain as well as the DTH reactivity to CBA/Ca renal tubular antigens mediated by lymphocytes from nephritic kdkd mice. These antigen-specific suppressor T cells are Lyt-2+, L3T4+, I-Jk+, genetically dominant and I-Jk restricted. Unfractionated spleen cells from young, prenephritic kdkd mice also demonstrate such suppressor function. Shortly preceding disease onset, however, net suppression is functionally bypassed by emergent contrasuppressor T cells. These regulatory cells are also Lyt-2+ and I-Jk+, and adhere both to the Vicia Villosa lectin and CBA/Ca TBM. By admixing these contrasuppressor cells with spleen cells from non-disease-prone CBA/Ca mice we were able to demonstrate the presence of DTH-reactive and nephritogenic effector cells in the latter population. Such nephritogenic effector cells could also be simply demonstrated after depletion of the suppressor cells with anti-I-Jk mAbs and complement. These findings support a role for contrasuppressor cells in the abrogation of tolerance to parenchymal self-antigens.
mesh_terms: D000367:Age Factors; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D005799:Genes, Dominant; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007684:Kidney Tubules / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D009395:Nephritis, Interstitial / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface