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 myeiold lineagein non-obese diabetic (NOD) mice. In this study we have characterizedthe phenotype and myeloid progenitor function of NOD bone marrow.Two hematopoletic differentiation antigens, Ly-6C and AA4.1,are expressed abnormally on NOD bone marrow cells. While multillneageerythromyeloid progenitor cells (day 12 CFU-S) are normal innumber in NOD mice, more differentiated myeloid progenitorsare deficient in their in vitro responses to IL-3, granulocyte/macrophagecolony-stimulating factor (GM-CSF), and IL-5. Since the diabetes-predisposingldd-5 gene of NOD mice maps close to the IL-1 receptor, we testedNOD bone marrow cells for a defect in synergy between IL-1 andIL-3; no defect was found. The defects in myelopoiesis describedhere may predispose the NOD mouse to autoimmunlty by impairingmacrophage maturation.