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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07132016-074224 |
| Date | 24 July 2016 |
| Creators | Stocks, Blair Taylor |
| Contributors | Daniel J. Moore, Alvin C. Powers, Edward Sherwood, Luc Van Kaer, Amy Major |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07132016-074224/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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