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.
Immunology Division, Department of Pathology, University of Cambridge, Cambridge, UK.
Richard J
RJ
Mellanby
Jenny M
JM
Phillips
Nicole M
NM
Parish
Anne
A
Cooke
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