Cutting Edge: Multiple autoimmune pathways in kd/kd mice.
The kidney disease (kd) mutation was transferred to a C57BL/6 (B6) background by selection for closely linked microsatellite markers. The resulting congenic strain, B6.kd, was mated with partners homozygous for targeted mutations of CD4, CD8, CD28, IL-2, recombinase-activating gene-1 (Rag-1), ICAM-1, or beta(2)-microglobulin. In most of the resulting double mutants, kidney disease occurred as readily and as severely as in the B6.kd controls, although disease occurred somewhat less frequently in age-matched CD28(-/-) kd/kd mice. Immunohistology demonstrated a predominance of macrophages in the lesions of B6.kd and most of the double mutants, with the remaining cells consisting of T cells and variable numbers of NK cells. In Rag-1(-/-) kd/kd, approximately 50% of infiltrating cells were macrophages, and approximately 50% were NK cells. These results suggest that the initial lesion caused by the mutant gene is intrinsic to the kidney and that the immune response that subsequently occurs can involve any one of several different cellular compositions.
Hancock
Wayne W
WW
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and the University of Philadelphia School of Medicine, Philadelphia, PA 19104, USA.
Tsai
Tsai-Lung
TL
Madaio
Michael P
MP
Gasser
David L
DL
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018106:CD28 Antigens / Q000235:genetics; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D016827:CD8 Antigens / Q000235:genetics; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D018106:CD28 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D018398:Homeodomain Proteins; D007376:Interleukin-2; D001613:beta 2-Microglobulin; D018799:Intercellular Adhesion Molecule-1; C064658:RAG-1 protein