Analyses of development of insulitogenic T lymphocytes in NOD mice by transplantation of bone marrow, thymus, and pancreas.

To estimate the functional participation of the insulitogenic genes in the development of insulitogenic lymphocytes, we attempted to induce insulitis in normal allogeneic BALB/c hosts by bone marrow transplantation from NOD mice. The development of the insulitogenic lymphocytes was histologically examined using the host's pancreas and pancreatic tissue from NOD mice which had been grafted under the renal capsules 2 weeks before sacrifice. Adult-thymectomized NOD mice that had been reconstituted with the thymus and bone marrow from NOD mice showed insulitis in both the host's pancreas and grafted pancreatic tissue from newborn NOD mice. When BALB/c mice were lethally irradiated and then reconstituted with NOD bone marrow cells, no insulitis developed in the pancreatic grafts from NOD and BALB/c mice or in the host's pancreas. Since the specificities and functions of T lymphocytes are controlled by the thymic microenvironment during the differentiation within the thymus, the thymus of BALB/c genotype may be responsible for the failure to induce the insulitogenic lymphocytes. Therefore, athymic BALB/c mice were reconstructed with bone marrow cells and thymus of NOD genotype. No insulitis developed, however, in either the host's pancreas or grafted pancreatic tissue. These results suggest that the bone marrow cells and thymus of NOD genotype are not sufficient to induce insulitogenic lymphocytes in the allogeneic BALB/c environment.