Autoimmune Diabetes and Transplantation Tolerance Induced by Costimulation Blockade in NOD Mice: a Dissertation
نویسنده
چکیده
..........................................................................................vi TABLE OF CONTENTS.........................................................................viii LIST OF FIGURES................................................................................xii ABBREVIATIONS................................................................................xiv INTRODUCTION..................................................................................1 OVERVIEW OF DIABETES MELLITUS.......................................................1 SOLID ORGAN TRANSPLANTATION............................................................3 Direct and indirect pathways of allorecognition.........................................3 Role of T cells................................................................................5 Role of NK cells..............................................................................7 Role of dendritic cells.......................................................................8 Role of B cells..............................................................................10 Role of macrophages.......................................................................10 CENTRAL AND PERIPHERAL TOLERANCE..............................................11 Central tolerance............................................................................11 Peripheral tolerance and costimulation blockade-based tolerance induction....................................................................................12 CD28/B7............................................................................14 CD40/CD154.........................................................................15 ICOS/B7h............................................................................16 OX40/OX40L.....................................................................17 41-BB/41-BBL.....................................................................18 CTLA-4.............................................................................19 PD-1.................................................................................20
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The Genetic Basis of Resistance to Transplantation Tolerance Induced by Costimulation Blockade in NOD Mice: a Dissertation
The NOD mouse is a widely studied model of type 1 diabetes. The loss of selftolerance leading to autoimmune diabetes in NOD mice involves at least 27 genetic loci. Curing type 1 diabetes in mice and humans by islet transplantation requires overcoming both allorejection and recurrent autoimmunity. This has been achieved with systemic immunosuppression, but tolerance induction would be preferable...
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OBJECTIVE NOD mice model human type 1 diabetes and are used to investigate tolerance induction protocols for islet transplantation in a setting of autoimmunity. However, costimulation blockade-based tolerance protocols have failed in prolonging islet allograft survival in NOD mice. RESEARCH DESIGN AND METHODS To investigate the underlying mechanisms, we studied the ability of costimulation bl...
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