Role of Natural Killer Cells in the Innate Immune System After Intraportal Islet Transplantation in Mice

Background

Both liver natural killer (NK) and NK T cells of the innate immune system play a crucial role in islet graft loss after intraportal islet transplantation, although a relationship between NK and NK T cells in islet loss has not been proven. In this study, we investigated the role of NK cells in the innate immune system in islet graft loss after intraportal islet transplantation.

Methods

To investigate the involvement of liver NK cells in islet destruction, we assessed the differences in graft survival after intraportal islet transplantation between CD1d^?/? diabetic mice and NK cell–depleted CD1d^?/? diabetic mice.

Results

The transplantation of 400 islets into the liver was sufficient to reverse hyperglycemia in wild-type diabetic mice (100%, 4/4). However, normoglycemia could not be achieved when 200 islets were transplanted (0%, 0/4). In contrast, intraportal transplantation of 200 islets in NK cell–depleted CD1d^?/? diabetic mice ameliorated hyperglycemia in 71% of cases (5/7), whereas transplantation of the same number of islets in CD1d^?/? diabetic mice did not (0%, 0/4). Histologic findings also confirmed that intact islets were observed in NK cell–depleted CD1d^?/? diabetic mice, but were difficult to observe in CD1d^?/? diabetic mice.

Conclusions

The involvement of liver NK cells in the innate immune system related to islet graft loss after intraportal islet transplantation is revealed by improved graft survival and function in NK cell–depleted CD1d^?/? diabetic mice. Our data reveal that regulation of NK cell activity is particularly important when insufficient islet numbers are used for transplantation.