Beta cell MHC class I is a late requirement for diabetes
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Hamilton-Williams, Emma
Palmer, Stephanie
Charlton, Brett
Slattery, Robyn
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National Academy of Sciences (USA)
Abstract
Type 1 diabetes occurs as a result of an autoimmune attack on the insulin-producing beta cells. Although CD8 T cells have been implicated both early and late in this process, the requirement for direct interaction between these cells and MHC class I on the beta cells has not been demonstrated. By using nonobese diabetic mice lacking beta cell class I expression, we show that both initiation and progression of insulitis proceeds unperturbed. However, without beta cell class I expression, the vast majority of these mice do not develop hyperglycemia. These findings demonstrate that a direct interaction between CD8 T cells and beta cells is not required for initiation or early disease progression. The requirement for class I on beta cells is a relatively late checkpoint in the development of diabetes.
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PNAS - Proceedings of the National Academy of Sciences of the United States of America