Journal article
Complete diabetes protection despite delayed thymic tolerance in NOD8.3 TCR transgenic mice due to antigen-induced extrathymic deletion of T cells
B Krishnamurthy, J Chee, G Jhala, S Fynch, KL Graham, P Santamaria, G Morahan, J Allison, D Izon, HE Thomas, TWH Kay
Diabetes | Published : 2012
DOI: 10.2337/db11-0948
Abstract
Prevention of autoimmunity requires the elimination of self-reactive T cells during their development in the thymus and maturation in the periphery. Transgenic NOD mice that overexpress islet-specific glucose 6 phosphatase catalytic subunit-related protein (IGRP) in antigen-presenting cells (NOD-IGRP mice) have no IGRP-specific T cells. To study the relative contribution of central and peripheral tolerance mechanisms to deletion of antigen-specific T cells, we crossed NOD-IGRP mice to highly diabetogenic IGRP 206-214 T-cell receptor transgenic mice (NOD8.3 mice) and studied the frequency and function of IGRP-specific T cells in the thymus and periphery. Peripheral tolerance was extremely eff..
View full abstractGrants
Funding Acknowledgements
B.K received a Career Development Award from the Juvenile Diabetes Research Foundation (JDRF) and a Centres of Clinical Research Excellence Fellowship from the National Health and Medical Research Council of Australia (NHMRC). K.L.G. received a postdoctoral fellowship from the JDRF and a Skip Martin Early Career Postdoctoral Fellowship from the Australian Diabetes Society. P.S. is a Scientist of the Alberta Heritage Foundation for Medical Research and received support from the Canadian Institutes of Health Research and the JDRF. H.E.T. received a Career Development Award from the NHMRC. T.W.H.K. received a Millennium Research Grant from Diabetes Australia, a program project grant from JDRF, and a program grant from NHMRC. St. Vincent's Institute receives support from the Operational Infrastructure Support Scheme of the Government of Victoria. The Julia McFarlane Diabetes Research Centre is supported by the Diabetes Association (Foothills).