Relationship between β cell mass of NOD donors and diabetes development of NOD-scid recipients in adoptive transfer system

Background - There is controversy about the way the β cell mass is reduced in type 1 diabetes. One view is that a gradual fall in β cell mass begins soon after the onset of insulitis. Another view is that a sudden wave of β cell destruction occurs just before the onset of diabetes. To clarify how the β cell mass is reduced, we performed adoptive transfer experiments and examined the relationship between the pancreatic status of NOD donors and the time taken to transfer diabetes into NOD-scid recipients. Methods - We killed 18-week-old female NOD mice (n = 20), removed their spleen, and transferred splenocytes into 5-week-old female NOD-scid mice (n = 60). The relationship between the pancreatic status of donors and the time taken to transfer diabetes into recipients was assessed. As pancreatic status, we measured Insulin content and severity of insulitis. Results - There was no linear correlation between the pancreatic status of donors and the time taken to transfer diabetes into recipients. NOD donors who needed 7 or more weeks to transfer diabetes in NOD-scid recipients had similar levels of insulin content or severity of insulitis as those of NOD donors who could not transfer diabetes. On the other hand, NOD donors who needed 6 or less weeks to transfer diabetes in recipients had similar levels of insulin content or severity of insulitis as those of diabetic NOD mice. Conclusions -According to our observations, β cell mass seems to be preserved until just before the onset of diabetes and decreased dramatically within a few weeks.