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Factors Controlling CD4 T Cell Differentiation Within the Intestine

Visperas, Anabelle Joyce
http://rave.ohiolink.edu/etdc/view?acc_num=case1397230785

Abstract Details

2014, Doctor of Philosophy, Case Western Reserve University, Molecular Medicine.
The immune system maintains a fine balance between immunity and tolerance. Uncontrolled immune activation may develop into autoimmune inflammation, while dysregulated immune tolerance can lead to increased susceptibility to infection. Therefore, mounting optimal immunity is a process involving multiple cell subsets, factors, and a tightly controlled collaboration between them. Within the gut, non-self antigens, both benign and pathogenic, constantly bombard the immune system. The immune system differentiates benign food antigens or commensal bacteria, for which immune tolerance is necessary, from pathogenic organisms, where protective immunity is preferred. Balance must be maintained especially within the gut. Inducible regulatory T cells (iTregs) are highly enriched within the gut tissue to maintain tolerance against benign antigens where ¿d T cells are also present. We demonstrate an immunoregulatory role for ¿d T cells in interfering with iTreg generation especially in the gut associated lymphoid tissues. This process may be important in controlling the balance between tolerance and reactivity within the gut. The production of IFN¿ by ¿d T cells can inhibit CD4 differentiation into iTregs. This balance may be critical, as breakdown in tolerance can lead to inflammatory responses to benign antigens. Adoptive transfer of nai¨ve CD4 T cells into immunodeficient mice develop colitis 4-6 weeks after transfer, a widely used animal model for chronic intestinal inflammation. IL-17-producing Th17 type effector cells are implicated in the pathogenesis of inflammatory bowel disease. However, a cellular mechanism that promotes colitogenic Th17 cell generation remains unclear. Transfer of CD4 T cells into immunodeficient mice lacking IL-27R expression was unable to induce colitis. While expansion of effector CD4 T cells remained similar, differentiation into the Th17 lineage was selectively impaired, correlating with a decreased production of Th17-promoting cytokines. We identified a novel proinflammatory role for IL-27 that targets antigen presenting cells to enhance production of Th17 promoting cytokines. In summary, many factors contribute to control of immune responses within the gut and when homeostasis is not maintained, inflammatory responses continue unabated. Defining cellular mechanisms involved in immunity and tolerance will offer key insight into the development of therapeutic approaches that target inflammation in the intestine and other tissues.
Booki Min, DVM, PhD (Advisor)
Alex Huang, MD, PhD (Committee Chair)
Robert Fairchild, PhD (Committee Member)
Carol de la Motte, PhD (Committee Member)
Bo Shen, MD (Committee Member)
129 p.
Immunology

Recommended Citations

Citations

  • Visperas, A. J. (2014). Factors Controlling CD4 T Cell Differentiation Within the Intestine [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1397230785

    APA Style (7th edition)

  • Visperas, Anabelle Joyce. Factors Controlling CD4 T Cell Differentiation Within the Intestine. 2014. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1397230785.

    MLA Style (8th edition)

  • Visperas, Anabelle Joyce. "Factors Controlling CD4 T Cell Differentiation Within the Intestine." Doctoral dissertation, Case Western Reserve University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1397230785

    Chicago Manual of Style (17th edition)

case1397230785
526
© 2014, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.