Both central and peripheral tolerance mechanisms play roles in diabetes prevention in NOD-E transgenic mice.
The non-obese diabetic (NOD) mouse spontaneously develops diabetes and is a widely used model of Type 1 Diabetes in humans. The major histocompatibility complex class II plays an important role in governing disease susceptibility in NOD mice. NOD mice express a rare I-A allele, I-A(g7), and do not express I-E molecules. Interestingly, transgenic NOD mice which express I-E (NOD-E) fail to develop diabetes although, the protective mechanism(s) are incompletely understood. Initially, we explored whether diabetes prevention was due to deletion of autoreactive T cells. Through adoptive transfer with depletion of CD25+ T cells, we demonstrated that autoreactive T cells were present in the periphery of NOD-E mice. Although, BDC2.5NOD T cells proliferated less in the pancreatic lymph nodes of NOD-E mice, we found that they transferred disease with a similar kinetic in NOD.scid and NOD-E.scid recipients suggesting that there was little difference in peripheral antigen presentation in NOD-E mice. We also found that there were no proportional or functional differences between NOD and NOD-E T regs. Our studies indicate that autoreactive T cells are present within the periphery of NOD-E mice but that these cells are present in low numbers suggesting that peripheral tolerogenic mechanisms are able to prevent them from inducing diabetes.
Mellanby
Richard J
RJ
Immunology Division, Department of Pathology, University of Cambridge, Cambridge, UK.
Phillips
Jenny M
JM
Parish
Nicole M
NM
Cooke
Anne
A
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005434:Flow Cytometry; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D053645:Interleukin-2 Receptor alpha Subunit