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Title page for ETD etd-07132016-074224


Type of Document Dissertation
Author Stocks, Blair Taylor
Author's Email Address blair.stocks@vanderbilt.edu
URN etd-07132016-074224
Title Dysregulated T-B Lymphocyte Collaboration in Autoimmunity Poses a Barrier to Transplant Tolerance
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Amy Major Committee Chair
Alvin C. Powers Committee Member
Daniel J. Moore Committee Member
Edward Sherwood Committee Member
Luc Van Kaer Committee Member
Keywords
  • T Regulatory Cells
  • Transplantation
  • Autoimmunity
  • Type 1 Diabetes
  • Lupus
  • Tolerance
Date of Defense 2016-07-11
Availability restricted
Abstract
Achieving transplant tolerance in the autoimmune environment will require targeting multiple immunologic dysregulations in T-B lymphocyte collaboration that drive the aggressive anti-graft response. At a biologic level, my findings reveal the necessity of overcoming B lymphocyte mediated restriction of CD4 Treg function, failed HSC mobilization, and enhanced T cell metabolism in achieving transplant tolerance in murine models of Type 1 Diabetes (T1D) and Systemic Lupus Erythematosus (SLE). At a cellular level, my dissertation demonstrates that specific failures in CD4 and CD8 Treg mediated suppression of the effector cell response in autoimmune T1D and SLE contributes to a generalized resistance to transplant tolerance observed in these strains. Overall, identification of and surmounting the key dysregulations in T-B cell collaboration that permit loss of tolerance in autoimmunity will advance the clinical potential of transplantation as a cure for autoimmune disease.
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