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CD25+ CTLA-4+ T Cell-Dependent Induction of Anergic CD25- T Cells Limits the Immune Response to H. pylori Infection Resulting in Mild Gastritis and Persistent Colonization

Anderson, Kathleen
http://rave.ohiolink.edu/etdc/view?acc_num=case1144332338

Abstract Details

2006, Doctor of Philosophy, Case Western Reserve University, Pathology.
Helicobacter pylori (H. pylori) is a gastric pathogen infecting more than half the world’s population. H. pylori infection induces gastric inflammation but the host fails to generate protective immunity. It has been established that infection lasts for the life of the host despite the induction of inflammation and adaptive immune responses. It has also previously demonstrated that protective immunity is CD4+ T cell-dependent while CD4+ T cells remain hyporesponsive during chronic infection. Therefore, we evaluated the immunologic mechanisms that contribute to the failure of the CD4+ T cells to promote active immunity to H. pylori in the murine model of H. pylori infection. We demonstrate here that the H. pylori-specific T cells are predominantly anergic. We provide in vitro and in vivo evidence that while CD25+ regulatory T cells are required to induce this anergic state in bystander CD25- cells, the CD25- T cells remain hyporesponsive even when the regulatory T cells have been removed. Interestingly, even CD25- cells that arise in the absence of regulatory T cells and therefore are capable of promoting eradication of H. pylori can be down-regulated when combined with regulatory T cells. These results demonstrate that CD25+ regulatory T cells not only influence naïve CD25- cells but may also limit the response of previously-activated CD25- cells. Finally, we address the mechanism by which the anergic state is induced by showing that CTLA-4 engagement on the surface of CD25+ regulatory T cells plays a critical role in the H. pylori immune response. These findings demonstrating functional inactivation are in accord with the success of therapeutic immunization in which protective immunity is permitted to develop in the face of active chronic inflammation resulting from initial infection. Based on data presented in this thesis, we hypothesize that CTLA-4 expression by CD25+ regulatory T cells induces anergy in bystander CD25- responder cells resulting in a reduced immune response and persistent infection.
Thomas Blanchard (Advisor)
170 p.
Health Sciences, Immunology
H. pylori; anergy; regulatory T cells; CTLA-4

Recommended Citations

Citations

  • Anderson, K. (2006). CD25+ CTLA-4+ T Cell-Dependent Induction of Anergic CD25- T Cells Limits the Immune Response to H. pylori Infection Resulting in Mild Gastritis and Persistent Colonization [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1144332338

    APA Style (7th edition)

  • Anderson, Kathleen. CD25+ CTLA-4+ T Cell-Dependent Induction of Anergic CD25- T Cells Limits the Immune Response to H. pylori Infection Resulting in Mild Gastritis and Persistent Colonization. 2006. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1144332338.

    MLA Style (8th edition)

  • Anderson, Kathleen. "CD25+ CTLA-4+ T Cell-Dependent Induction of Anergic CD25- T Cells Limits the Immune Response to H. pylori Infection Resulting in Mild Gastritis and Persistent Colonization." Doctoral dissertation, Case Western Reserve University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=case1144332338

    Chicago Manual of Style (17th edition)

case1144332338
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© 2006, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.