Search

The nonobese diabetic mouse in a model of spontaneous development of autoimmune type I diabetes. The disease can be induced in young, irradiated recipients by injecting splenic T-cells from diabetic donors. The adoptive transfer of diabetes requires the presence of both CD4+ and CD8+ splenic T-cell subsets. To test whether diabetogenic cells distribute in other lymphoid organs of diabetic mice, we first analyzed lymph node cells. Lymph node cells were much less efficient in transferring diabetes than splenocytes. This inefficacious transfer was not attributable to the absence of hematopoietic precursors or a lack of macrophages. Lymph node cells did not protect from the transfer of diabetes by splenocytes, indicating the absence of suppressor cells. Although CD8+ lymph node T-cells seemed functionally comparable to CD8+ splenocytes, CD4+ lymph node T-cells failed to cooperate with CD8+ splenocytes to transfer diabetes. Our study suggests that diabetogenic cells are not evenly distributed in the different lymphoid organs. This may reflect a differential migration pattern of pathogenic T-cells in this animal model.

It is well established that the NOD mouse develops T-cell-dependent autoimmune type I diabetes that is abolished by neonatal Tx and enhanced by Tx at weaning. In a previous study, we demonstrated that the NOD thymus displays various abnormalities in the microenvironmental compartment, including abnormal distribution of epithelial cell subsets, precocious decline in thymic hormone production and formation of giant PVS. These latter structures present an internal ECM-containing network filled with T-cells and to a lesser extent B-cells. Herein we have investigated further the giant PVS and particularly the origin of the T-cells that colonize these structures. The thymic origin of intra-PVS T-cells was ascertained by distinct protocols. First, sublethal X-ray irradiation or HC treatment leading to cortical thymocyte depletion showed that intra-PVS lymphocytes were resistant, similar to medullary thymocytes. Second, adoptive transfer experiments that used newborn or adult irradiated Thy-1 congenic recipients demonstrated that intra-PVS accumulation of T-cells did not result from the reentry of peripheral mature T-cells into the thymus. Third, kinetic studies that used BrdUrd pulse chase revealed that labeled intra-PVS cells appear late, simultaneously with medullary thymocytes, and remain only transiently within the PVS. Thus, the kinetics of T-cell reconstitution of PVS was compatible with the progressive differentiation of T-cell precursors originating from the thymic cortex. In this respect, the giant PVS of the NOD mouse thymus may represent a useful model to study the relationships between trafficking thymocytes and ECM proteins.