The Role of MHC-II Dependent Events in the Suppression Mediated by CD4+Foxp3+ Regulatory T cells

Hdl Handle:
http://hdl.handle.net/10675.2/317604
Title:
The Role of MHC-II Dependent Events in the Suppression Mediated by CD4+Foxp3+ Regulatory T cells
Authors:
Mmanywa, Faith Daima
Abstract:
CD4+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.
Affiliation:
Department of Medicine
Issue Date:
Aug-2008
URI:
http://hdl.handle.net/10675.2/317604
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/304402769?accountid=12365
Type:
Dissertation
Language:
en_US
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorMmanywa, Faith Daimaen
dc.date.accessioned2014-05-29T14:04:25Z-
dc.date.available2014-05-29T14:04:25Z-
dc.date.issued2008-08-
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.en
dc.language.isoen_USen
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/304402769?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.-
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.-
dc.description.committeeMunn, David; Mellor, Andrew; Horuzsko, Anatolij; He, Yukai; Phillips, Andrew.-
dc.description.degreeDoctor of Philosophy (Ph.D.)-
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