Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells.
Open Access
- 1 November 1990
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 87 (21), 8341-8344
- https://doi.org/10.1073/pnas.87.21.8341
Abstract
Transplantation of bone marrow cells from nonobese diabetic (NOD) mice, a model for type 1 diabetes mellitus, to C3H/HeN mice, which express I-E alpha molecules and have aspartic acid at residue 57 of the I-A beta chain, 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)F1 mice, 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)F1 mice 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.This publication has 25 references indexed in Scilit:
- The unique nucleotide sequence of the Aβ gene in the NOD mouse is shared with its nondiabetic sister strains, the ILI and the CTS mouseInternational Immunology, 1990
- The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique.Proceedings of the National Academy of Sciences, 1987
- Sequence analysis and structure-function correlations of murine q, k, u, s, and f haplotype I-A beta cDNA clones.Proceedings of the National Academy of Sciences, 1986
- Prevention of type I diabetes in nonobese diabetic mice by allogenic bone marrow transplantation.Proceedings of the National Academy of Sciences, 1985
- Rationale for bone marrow transplantation in the treatment of autoimmune diseases.Proceedings of the National Academy of Sciences, 1985
- ABNORMAL STEM-CELLS IN AUTOIMMUNE-PRONE MICE ARE RESPONSIBLE FOR PREMATURE THYMIC INVOLUTION1985
- Murine Models of Systemic Lupus ErythematosusAdvances in Immunology, 1985
- Isolation of murine pluripotent hemopoietic stem cells.The Journal of Experimental Medicine, 1984
- Reciprocal transfer of abnormalities in clonable B lymphocytes and myeloid progenitors between NZB and DBA/2 mice.The Journal of Immunology, 1981
- Transplantation of Autoimmune Potential. I. Development of Antinuclear Antibodies in H-2 Histocompatible Recipients of Bone Marrow from New Zealand Black MiceProceedings of the National Academy of Sciences, 1974