Bone marrow abnormalities in the non-obese diabetic mouse.
Several lines of evidence point to abnormalities of the phenotype, cytokine responses, and function of cells of the myeloid lineage in non-obese diabetic (NOD) mice. In this study we have characterized the phenotype and myeloid progenitor function of NOD bone marrow. Two hematopoietic differentiation antigens, Ly-6C and AA4.1, are expressed abnormally on NOD bone marrow cells. While multilineage erythromyeloid progenitor cells (day 12 CFU-S) are normal in number in NOD mice, more differentiated myeloid progenitors are deficient in their in vitro responses to IL-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), and IL-5. Since the diabetes-predisposing Idd-5 gene of NOD mice maps close to the IL-1 receptor, we tested NOD bone marrow cells for a defect in synergy between IL-1 and IL-3; no defect was found. The defects in myelopoiesis described here may predispose the NOD mouse to autoimmunity by impairing macrophage maturation.
Langmuir
P B
PB
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.
Bridgett
M M
MM
Bothwell
A L
AL
Crispe
I N
IN
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D000950:Antigens, Ly / Q000032:analysis / Q000235:genetics; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology*; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D016130:Immunophenotyping; D007378:Interleukins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008810:Mice, Inbred C57BL / Q000276:immunology; D016688:Mice, Inbred NOD / Q000235:genetics / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000235:genetics
D000943:Antigens, Differentiation; D000950:Antigens, Ly; D007378:Interleukins; D017472:Receptors, Interleukin-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor