Beta cell MHC class I is a late requirement for diabetes.
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.
John Curtin School of Medical Research, Australian National University, Canberra 2601, Australia.
Emma E
EE
Hamilton-Williams
Stephanie E
SE
Palmer
Brett
B
Charlton
Robyn M
RM
Slattery
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006943:Hyperglycemia / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011995:Recombination, Genetic
D017931:DNA Primers; D015395:Histocompatibility Antigens Class I