DEVELOPMENT OF INSULIN-DEPENDENT DIABETES-MELLITUS IN [(NOD+BALB C)-]NOD] MIXED ALLOGENEIC BONE-MARROW CHIMERAS/

To examine the possibility that the bone marrow cells of BALB/c genoty pe interfere with the development of insulitis and diabetes in NOD mic e, we transplanted BALB/c bone marrow cells mixed with NOD bone marrow cells into NOD mice. The [(NOD + BALB/c) --> NOD] chimeras developed insulitis and diabetes, indicating that BALB/c bone marrow cells do no t interfere with the development of the disease in NOD mice. Surprisin gly, these mice have been reconstituted with only NOD hematolymphoid c ells. When the pancreatic tissues from newborn NOD and BALB/c mice wer e grafted into [(NOD+BALB/c) --> NOD] chimeras, the BALB/c pancreatic tissues were rejected, whereas the NOD) graft showed insulitis. Furthe rmore, the spleen cells of the chimeras showed responsiveness to BALB/ c spleen cells in mixed lymphocyte reaction and erated cytotoxic T lym phocytes specific for the H-2(d) and third party targets. These findin gs indicate that the hematolymphoid cells (including hemopoietic stem cells) of NOD mice are more resilient than those of normal BALB/c mice , and that insulin-dependent diabetes mellitus will recur after bone m arrow transplantation unless the hematolymphoid cells of NOD mice are completely destroyed by irradiation.