Absence of Insulitis and Overt Diabetes in Athymic Nude Mice with NOD Genetic Background

Prolonged and effective blockade of tumor necrosis factor activity through adenovirus-mediated gene transfer.

“…For some time, questions have been raised concerning the action of TNF in chronic autoimmune states (30)(31)(32), such as systemic lupus erythematosus [modeled by the NZW/NZB F1 hybrid mouse (33)(34)(35)] and type 1 diabetes [modeled by mice of the nonobese diabetic (NOD) strain (36)]. Whereas passive immunization of such animals might not be practical given the long latent period of the disease, the use of the TNF inhibitor expression system described here will allow an assessment of the importance of this and other cytokines in the pathogenesis of autoimmunity.…”

The phenotype of lymphoid cells and thymic epithelium correlates with development of autoimmune insulitis in NOD in equilibrium with C57BL/6 allophenic chimeras.

“…In these mice overt diabetes develops spontaneously in a majority of female mice and less frequently in male mice. As in human insulin-dependent diabetes mellitus, development of overt diabetes in NOD mice is preceded by infiltration of lymphoid cells into the pancreatic islets and is observed only after massive destruction of insulin-producing f3 cells (2).…”

Reactive oxygen intermediates in autoimmune islet cell destruction of the NOD mouse induced by peritoneal exudate cells (rich in macrophages) but not T cells

“…NOD mice exhibit massive infiltrates of lymphoid cells and macrophages into pancreatic islets (insulitis) prior to complete betacell destruction, and insulitis appears as early as 5 weeks of age. Makino and co-workers [4] have shown that T cells play an important role in the development of insulitis and diabetes in nude NOD mice. The major infiltrating cell populations in the insulitis lesion are CD4 § (L3T4, helper) and CD8 § (Ly2, cytotoxic/suppressor) T cells, and macrophages [5].…”