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 genotype interfere with the development of insulitis and diabetes in NOD mice, 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 not interfere with the development of the disease in NOD mice. Surprisingly, these mice have been reconstituted with only NOD hematolymphoid cells. When the pancreatic tissues from newborn NOD and BALB/c mice were grafted into [(NOD + BALB/c) --> NOD] chimeras, the BALB/c pancreatic tissues were rejected, whereas the NOD graft showed insulitis. Furthermore, the spleen cells of the chimeras showed responsiveness to BALB/c spleen cells in mixed lymphocyte reaction and generated cytotoxic T lymphocytes specific for the H-2d and third party targets. These findings 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 marrow transplantation unless the hematolymphoid cells of NOD mice are completely destroyed by irradiation.