Organ-Specific and Systemic Autoimmune Diseases Originate from Defects in Hematopoietic Stem Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 21; pp. 8341 - 8344
• Main Authors: Ikehara, Susumu, Kawamura, Masayo, Takao, Fumiyuki, Inaba, Muneo, Yasumizu, Ryoji, Than, Soe, Hisha, Hiroko, Sugiura, Kikuya, Koide, Yukio, Yoshida, Takato O., Ida, Tatsuya, Imura, Hiroo, Good, Robert A.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.11.1990; National Acad Sciences
• Subjects: Animals; Antibodies; Antibodies, Monoclonal; Autoimmune diseases; Autoimmune Diseases - immunology; Autoimmune Diseases - pathology; Autoimmunity (experimental aspects and models); Biological and medical sciences; Bone marrow cells; Bone Marrow Transplantation - immunology; Diabetes mellitus; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - pathology; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Fundamental immunology; H-2 Antigens - analysis; Hematopoietic Stem Cells - immunology; Islets of Langerhans - immunology; Islets of Langerhans - pathology; Male; Mice; Mice, Inbred C3H; Mice, Inbred Strains; Mice, Mutant Strains; Platelets; Stem cells; T lymphocytes; Transplantation; Type 1 diabetes mellitus; Autoimmunity; Immunohistochemistry; Flow cytometry; Animal model; Induction; Pathogenesis; Stem cell; Rodentia; Hematopoietic cell; Autoimmune disease; Histology; Vertebrata; Mammalia; Mouse; Bone marrow; Graft; Chimera
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.21.8341

Transplantation of bone marrow cells from nonobese diabetic (NOD) mice, a model for type 1 diabetes mellitus, to C3H/HeN mice, which express I-Eα molecules and have aspartic acid at residue 57 of the I-Aβchain, induced insulitis followed by overt diabetes in the recipient C3H/HeN mice more than 40 weeks after bone marrow transplantation. When cyclosporin A, which perturbs T-cell functions, was injected intraperitoneally into [NOD → C3H/HeN] chimeric mice daily for 1 month, the chimeric mice developed insulitis and overt diabetes within 20 weeks following bone marrow transplantation. Transplantation of bone marrow cells from (NZW x BXSB)F1mice, which develop lupus nephritis, myocardial infarction, and idiopathic thrombocytopenic purpura, into C3H/HeN or C57BL/6J mice induced in the recipient strains both lupus nephritis and idiopathic thrombocytopenic purpura more than 3 months after transplantation. Transplantation of a stem-cell-enriched population from (NZW x BXSB)F1mice into normal mice also induced autoimmune disease in the recipients. These results indicate that both systemic autoimmune disease and organ-specific autoimmune disease originate from defects that reside within the stem cells; the thymus and environmental factors such as sex hormones appear to act only as accelerating factors.