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dc.contributor.authorMmanywa, Faith Daima
dc.date.accessioned2014-05-29T14:04:25Z
dc.date.available2014-05-29T14:04:25Z
dc.date.issued2008-08en
dc.identifier.urihttp://hdl.handle.net/10675.2/317604
dc.description.abstractCD4+Foxp3+ regulatory T cells (Tregs) and antigen presenting cells (APCs) play an important role in maintaining peripheral tolerance but are otherwise exploited by tumors to create a state of unresponsiveness towards tumor antigens. The mechanisms of Treg mediated suppression are still not well understood. This work seeks to elucidate the role of major histocompatibility complex class II (MHC-II) dependent events in CD4+Foxp3+ Treg mediated suppression. The studies described here take advantage of novel conditional MHC-II deficient mice, which lack expression of MHC-II on peripheral APCs but still maintain their own naïve CD4 T cells and Tregs. In an in vitro system antigen-specific Tregs suppress CD8 T cell proliferation and effector molecule production in an antigen-specific and MHC-II dependent manner. In vivo, MHC-II deficiency resulted in a delay in tumor progression that was CD8 T cell dependent. We further describe two in vivo models in which the role of MHC-II dependent events in Treg mediated suppression can be tested. Therefore, a better understanding of Treg mediated suppression in the context of tumor-induced tolerance could provide potential strategies that could be utilized for anti-tumor immunotherapy.
dc.language.isoen_USen
dc.relation.urlhttp://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/304402769?accountid=12365en
dc.subjectMHC-IIen
dc.subjectRegulatory T Cellsen
dc.subjectAntigen Presenting Cellsen
dc.subjectTumor-Induced Toleranceen
dc.titleThe Role of MHC-II Dependent Events in the Suppression Mediated by CD4+Foxp3+ Regulatory T cellsen
dc.typeDissertationen
dc.contributor.departmentDepartment of Medicineen
dc.description.advisorKoni, Pandelakis A.en
dc.description.degreeDoctor of Philosophy (Ph.D.)en
dc.description.committeeMunn, David; Mellor, Andrew; Horuzsko, Anatolij; He, Yukai; Phillips, Andrew.en
html.description.abstractCD4+Foxp3+ regulatory T cells (Tregs) and antigen presenting cells (APCs) play an important role in maintaining peripheral tolerance but are otherwise exploited by tumors to create a state of unresponsiveness towards tumor antigens. The mechanisms of Treg mediated suppression are still not well understood. This work seeks to elucidate the role of major histocompatibility complex class II (MHC-II) dependent events in CD4+Foxp3+ Treg mediated suppression. The studies described here take advantage of novel conditional MHC-II deficient mice, which lack expression of MHC-II on peripheral APCs but still maintain their own naïve CD4 T cells and Tregs. In an in vitro system antigen-specific Tregs suppress CD8 T cell proliferation and effector molecule production in an antigen-specific and MHC-II dependent manner. In vivo, MHC-II deficiency resulted in a delay in tumor progression that was CD8 T cell dependent. We further describe two in vivo models in which the role of MHC-II dependent events in Treg mediated suppression can be tested. Therefore, a better understanding of Treg mediated suppression in the context of tumor-induced tolerance could provide potential strategies that could be utilized for anti-tumor immunotherapy.


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