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dc.contributor.authorManlapat, Anna Katrina
dc.date.accessioned2020-04-08T23:12:31Z
dc.date.available2020-04-08T23:12:31Z
dc.date.issued2006-04
dc.identifier.urien
dc.identifier.urihttp://hdl.handle.net/10675.2/623232
dc.description.abstract!DO-mediated tryptophan depletion inhibits T cell responses in vitro and in vivo. This work investigates the role of !DO-expressing dendritic cells (DCs) in regulating T c_ell responses. To determine the role of !DO-expressing DCs in the regulation of T cell immup.ity, IDO-transfected DCs and IDO transgenic mice over-expressing IDO specifically in DCs were_ generated, and effects of IDO over-expression on T cell stimulatory functions of DCs were assessed. ·Results show that inhibition of T cell proliferation in vivo_ requires induction of IDO expression in DCs by CTLA4-Ig rather than constitutive over-expression of IDO. In addition, we have recently shown that IDO induction leading to T cell suppression is mediated by CTLA4-Ig ligation of B7 molecules on a minor subset of DCs that express the surface marker CD 19. Interferon-a (IFNa) was rapidly produced by CD19+ DCs after CTLA4-Ig treatment in vitro, _and signaling via IFN a receptors (IFNAR) was esse:μtial for activation of the transcription factor STATl, while IFNy signaling was not. To further understand the role of IDOexpressing DCs, DCs from !DO-deficient mice were treated in vitro and in vivo with CTLA4-Ig. In addition, IDO-wildtype mice were also treated in vitro with CTLA4-Ig in the presence of the pharmacological IDO inhibitor 1-methyl-tryptophan (1-MT). IFNa production in response to CTLA4-Ig was detected in IDO-WT but not in IDO-KO DCs or IDO-WT treated with 1-MT. These results show that IDO is both upstream and ~ownstream of IFNa production following B7 ligation. This study provides a better understanding of the role of IDO in antigen-presenting cells and evaluates the tolerogenic activity of APCs.en_US
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.en_US
dc.subjectIndoleamine 2en_US
dc.subjectDendritic Cellsen_US
dc.subjectT Cell Suppressionen_US
dc.titleThe effects of transforming growth factor - beta on macromolecular synthesis by human gingival and periodontal ligament fibroblastsen_US
dc.typeDissertationen_US
dc.typeDissertationen
dc.contributor.departmentDepartment of Oral Biologyen_US
dc.description.advisorMellor, Andrew;en_US
dc.description.degreeDoctor of Philosophyen_US
dc.description.committeeBollag, Wendy; Koni, Pandelakis; Ignatowicz, Lezek; Smith, Sylvia;en_US
refterms.dateFOA2020-04-08T23:12:31Z


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