PREVENTION OF AUTOIMMUNITY IN NONOBESE DIABETIC (NOD) MICE BY NEONATAL TRANSFER OF ALLOGENEIC THYMIC MACROPHAGES

Nonobese diabetic (NOD) mice spontaneously develop insulin dependent d iabetes mellitus. The disease results from an autoimmune process which involves mononuclear cells surrounding and eventually infiltrating th e pancreatic islets of Langerhans. Macrophages are thought to be the f irst cells to infiltrate the islets and are actively involved in the d isease process because diabetes is prevented if host macrophages are d epleted or inactivated. Several lines of evidence also suggest that NO D macrophages are phenotypically and Functionally abnormal. In this st udy, allogeneic (CBA) macrophages derived from the thymus were inocula ted into newborn NOD mice and these were followed for more than 250 da ys. Spontaneous diabetes was significantly reduced in female NOD mice (6% diabetic versus 45% of controls). Insulitis was also significantly reduced in both male and female mice compared to their control counte rparts, and in most cases there were virtually no inflammatory cells i n the pancreas. Allogeneic skin grafting and mixed leukocyte cultures indicated that the recipients were not tolerant of donor antigens, and donor-derived cells were not detected in the lymphoid tissues by eith er flow cytometry or immunohistochemistry. The results show that macro phages from diabetes-resistant donors will prevent insulitis and diabe tes in most recipients, however, the mechanism for the protection is u nclear, but does not appear to be due to long-term tolerance induction .