Indoleamine 2,3 -Dioxygenase Activity Suppresses T Ceil Responses

Hdl Handle:
http://hdl.handle.net/10675.2/346579
Title:
Indoleamine 2,3 -Dioxygenase Activity Suppresses T Ceil Responses
Authors:
Johnson, Theodore S.
Abstract:
Cells expressing indoleamine 2,3-dioxygenasc (IDO) inhibit proliferation of human T cells in vitro and protect murine fetuses from lethal attack by maternal T cells in vivo. This work investigates the hypothesis that IDO activity suppresses T cell responses. To test the prediction that pharmacological inhibition o f IDO enhances murine T cell responses in vivo, splenocytes from H-2Kb-specific T cell receptor transgenic (BM3) mice were injected into H-2Kb-expressing (CBK) recipients. As predicted, CD8+ T cell responses were augmented by 1-methyl-Dx-tryptophan (1-MeTrp) treatment o f recipient CBK mice, but only when BM3 donor T cells were derived from male mice. To further evaluate the prediction that IDO-expressing antigen presenting cells (APCs) inhibit antigen-specific T cell responses, we prepared IDO- and vectortransfected murine tumor cells expressing H-2Kb. BM3 T cell proliferation was diminished in co-cultures with IDO-transfected MCS7G cells, relative to vcctortransfected MCS7G cells. Furthermore, IDO-transfected MCS7G cells failed to prime H-2b-specific recall responses in allogeneic CBA mice unless co-administered with 1-MeTrp or endotoxin adjuvant. These results show that IDO-expressing APCs inhibit murine T cell responses in vitro and in vivo, and demonstrate the efficacy o f 1-MeTrp treatment in reversing the effects o f murine IDO-mediated T cell suppression in vivo.
Affiliation:
GRU Cancer Center
Issue Date:
Jun-2002
URI:
http://hdl.handle.net/10675.2/346579
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/305503320?accountid=12365
Type:
Dissertation
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorJohnson, Theodore S.en
dc.date.accessioned2015-03-13T03:02:01Zen
dc.date.available2015-03-13T03:02:01Zen
dc.date.issued2002-06en
dc.identifier.urihttp://hdl.handle.net/10675.2/346579en
dc.description.abstractCells expressing indoleamine 2,3-dioxygenasc (IDO) inhibit proliferation of human T cells in vitro and protect murine fetuses from lethal attack by maternal T cells in vivo. This work investigates the hypothesis that IDO activity suppresses T cell responses. To test the prediction that pharmacological inhibition o f IDO enhances murine T cell responses in vivo, splenocytes from H-2Kb-specific T cell receptor transgenic (BM3) mice were injected into H-2Kb-expressing (CBK) recipients. As predicted, CD8+ T cell responses were augmented by 1-methyl-Dx-tryptophan (1-MeTrp) treatment o f recipient CBK mice, but only when BM3 donor T cells were derived from male mice. To further evaluate the prediction that IDO-expressing antigen presenting cells (APCs) inhibit antigen-specific T cell responses, we prepared IDO- and vectortransfected murine tumor cells expressing H-2Kb. BM3 T cell proliferation was diminished in co-cultures with IDO-transfected MCS7G cells, relative to vcctortransfected MCS7G cells. Furthermore, IDO-transfected MCS7G cells failed to prime H-2b-specific recall responses in allogeneic CBA mice unless co-administered with 1-MeTrp or endotoxin adjuvant. These results show that IDO-expressing APCs inhibit murine T cell responses in vitro and in vivo, and demonstrate the efficacy o f 1-MeTrp treatment in reversing the effects o f murine IDO-mediated T cell suppression in vivo.en
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/305503320?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.en
dc.subjectAntigen Presenting Cellen
dc.subjectBM3en
dc.subjectindoleamine 2,3 dioxygenaseen
dc.subjectMC57Gen
dc.subject1-methyl-Dx-tiyptophanen
dc.subjectT cellen
dc.titleIndoleamine 2,3 -Dioxygenase Activity Suppresses T Ceil Responsesen
dc.typeDissertationen
dc.contributor.departmentGRU Cancer Centeren
cr.approval.ethicalhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/305503320?accountid=12365en
dc.description.advisorMellor, Andrewen
dc.description.committeeBollag, Wendy; Koni, Lak; Moskophidis, Dimi; Munn, Daviden
dc.description.degreeDoctor of Philosophy (Ph.D.)en
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