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Targeting Signal 1 of T cell Activation to Restore Self Tolerance in Type 1 Diabetes


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Targeting Signal 1 of T cell Activation to Restore Self Tolerance in Type 1 Diabetes
Table of Contents
Abstract
Acknowledgements
Table of Contents
List of Tables
List of Figures
List of Abbreviations
1 Introduction and Literature Review
1.1 Introduction
1.2 T cell Development and Central Tolerance
1.3 Peripheral T cell Activation, Differentiation, and Tolerance
1.4 Molecular Regulation of T cell Responses
1.5 The Pathogenesis of Type 1 Diabetes
1.6 Preclinical and Clinical Trials of Immune Therapies for Type 1 Diabetes
1.7 Summary and Hypothesis
2 Materials and Methods
2.1 Mice
2.2 Reagents
2.3 Adoptive Transfer and Stimulation of CFSE-labeled OT-I or OT-II cells
2.4 OT-I and OT-II cell Cultures
2.5 Measurement of CD3 Expression on T cells
2.6 Acute Type 1 Diabetes in RIP-OVAhi mice
2.7 Measurement of Cytokines in Serum
2.8 Type 1 Diabetes in NOD mice
2.9 Intraperitoneal Glucose Tolerance Test
2.10 Measurement of Serum Insulin Levels
2.11 Islet Histology and Scoring
2.12 Skin Transplantation in NOD mice
2.13 Immune cell Subset Analysis by Flow Cytometry
2.14 Quantitative Polymerase Chain Reaction Array Analysis of T cells
2.15 Statistical Analyses
3 Antibody Targeting the TCRβ-chain Selectively Abrogates Antigen-specific T cell Responses
4 Transient Treatment with Anti-TCRβ mAb Restores Self-tolerance in Diabetic NOD mice
5 Mechanistic Insights into the Anti-TCRβ mAb Induced Tolerance in Type 1 Diabetes
6 Discussion and Conclusions
6.1 Discussion
6.2 Future Directions
6.3 Conclusions
References
Appendix A Supplementary Material 
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