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The Role of Bim in Determining Thymic and Peripheral T Cell Fate

Li, Kun-Po, M.S.
http://orcid.org/0000-0002-8872-3814
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491560488232425

Abstract Details

2017, PhD, University of Cincinnati, Allied Health Sciences: Communication Sciences and Disorders - Distance Learning.
T cells play a critical role in promoting the clearance of pathogens and providing protective immunity to re-infection. T cells also provide immune surveillance against tumor cells. However, these responses must be restrained as excess or uncontrolled T cells can be pathologic, resulting in lymphatic neoplasia or autoimmune disease. Therefore, maintaining T cell homeostasis is essential to proper functioning of the adaptive immune system. Homeostasis is temporarily disturbed when T cells encounter antigen and undergo massive proliferation, and restored by the regulated induction of apoptosis, driven largely by the pro-apoptotic Bcl-2 family member, Bim. In addition to its role in controlling peripheral T cell homeostasis, Bim also restores homeostasis during thymocyte proliferation. In this dissertation, we aimed to further understand the role of Bim in restoring T cell homeostasis after substantial T cell proliferation in the thymus and the periphery. The results are described here in the form of two research articles, one has been published and the other is in preparation. In the final chapter, we discuss the potential research directions in the future. Finally, two published works that I authored, a literature review which focuses on the impact of cell death on T cell homeostasis, and an original research article which investigates the epigenetic regulation of memory T cell differentiation, are attached as Appendices. In the first Chapter, we review the literature about how Bim regulates T cell homeostasis and provide the relevant background and rationale for the research described in this dissertation. In Chapter II, we report our investigation of how Bim limits the development and TCR repertoire of agonist-selected T cells. This work has been published in the Journal of Immunology. In Chapter III, we found that TCR affinity and stimulation strength are correlated with Bim expression levels and memory generation. This work will be submitted for publication in the near future. In Chapter IV, the novel and significant findings in this dissertation are described. This chapter addresses how our studies add to the gaps in knowledge proposes several potential new research directions, new hypotheses that have emerged from this work, as well as describes experimental approaches to tests these hypotheses. Finally, one literature review article and one research article which I contributed as a co-first author are included in the Appendices. The review article focuses on the role of cell death and T cell homeostasis, with a particular emphasis on Bcl-2 family members, with potential clinical application. This review is published in Immunological Reviews. The research article includes our work on how DNA methyltransferase 3a limits memory CD8+ T cell differentiation. This article is published in the Proceedings of the National Academy of Sciences. The studies included in this dissertation increase our understanding in Bim-mediated control of T cell homeostasis in both the thymus and the periphery. Our data also provide new insights into the studies of the development of intestinal intraepithelial lymphocytes, regulation of TCR repertoire, CD8+ T cell differentiation, and the epigenetic regulation of CD8+ T cell memory development.
David Hildeman|, Ph.D. (Committee Chair)
Artem Barski, Ph.D. (Committee Member)
H. Grimes, Ph.D. (Committee Member)
Michael Jordan, M.D. (Committee Member)
David| Plas, Ph.D. (Committee Member)
Harinder Singh, Ph.D. (Committee Member)
321 p.
Immunology
T cell; thymocyte; apoptosis; immunology; cell development; Bim

Recommended Citations

Citations

  • Li, K.-P. (2017). The Role of Bim in Determining Thymic and Peripheral T Cell Fate [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491560488232425

    APA Style (7th edition)

  • Li, Kun-Po. The Role of Bim in Determining Thymic and Peripheral T Cell Fate. 2017. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491560488232425.

    MLA Style (8th edition)

  • Li, Kun-Po. "The Role of Bim in Determining Thymic and Peripheral T Cell Fate." Doctoral dissertation, University of Cincinnati, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1491560488232425

    Chicago Manual of Style (17th edition)

ucin1491560488232425
568
© 2017, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.