Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells.
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.
Ikehara
S
S
First Department of Pathology, Kansai Medical University, Osaka, Japan.
Kawamura
M
M
Takao
F
F
Inaba
M
M
Yasumizu
R
R
Than
S
S
Hisha
H
H
Sugiura
K
K
Koide
Y
Y
Yoshida
T O
TO
D000818:Animals; D000911:Antibodies, Monoclonal; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006183:H-2 Antigens / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens