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The Mannose receptor induces T cell tolerance via inhibition of CD45 and up-regulation of CTLA-4

dc.contributor.advisorBurgdorf, Sven
dc.contributor.authorSchütte, Verena
dc.date.accessioned2020-04-19T20:12:35Z
dc.date.available2020-04-19T20:12:35Z
dc.date.issued28.03.2014
dc.identifier.urihttp://hdl.handle.net/20.500.11811/6054
dc.description.abstractThe present study proves that the mannose receptor (MR) bears beside its function as endocytic receptor a second responsibility namely the induction of tolerance.
The results of our experiments show that the decision, whether this immune-suppressive effect is carried out depends on the inflammatory status of the surrounding milieu. Whereas at steady-state conditions the MR has a tolerogenic effect during activation of CD8+ T cells, this suppressive phenotype is overcome under inflammatory conditions. Thereby, the MR resembles a molecular switch between tolerance induction on the one hand and allowance or even mediating immunity by antigen-uptake on the other hand.
The investigations of this thesis shed light into the underlying molecular mechanism of the MR-mediated induction of tolerance. The MR on DCs can bind to the tyrosine phosphatase CD45 on the T cell surface. This interaction leads to inhibition of its phosphatase activity, which is responsible for a reduced cytotoxic capacity of activated CD8+ T cells. The executive molecule in this process is the inhibitory protein cytotoxic T-lymphocyte antigen 4 (CTLA-4), being up-regulated upon inactivation of CD45.
After maturation of the DCs with the inflammatory molecule CpG, the immune suppressive effect of the MR is overcome and a robust immune response is initiated. The findings of this study pinpoint this effect to the abolished expression of CTLA-4. It is furthermore shown that signaling events via the co-stimulatory molecule CD28 are sufficient to suppress CTLA-4 up-regulation. Hence, a potent cytotoxic CD8+ T cell response is induced.
Finally, it can be demonstrated that the tolerogenic effect of the MR as well as its molecular mechanism also holds true in vivo.
dc.language.isoeng
dc.rightsIn Copyright
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectMannose-Rezeptor
dc.subjectToleranz
dc.subjectCytotoxicity
dc.subjectIFN-gamma
dc.subjectCTLA4
dc.subjectCD45
dc.subjectMannose receptor
dc.subjecttolerance
dc.subjectZytotoxizität
dc.subject.ddc500 Naturwissenschaften
dc.subject.ddc570 Biowissenschaften, Biologie
dc.subject.ddc610 Medizin, Gesundheit
dc.titleThe Mannose receptor induces T cell tolerance via inhibition of CD45 and up-regulation of CTLA-4
dc.typeDissertation oder Habilitation
dc.publisher.nameUniversitäts- und Landesbibliothek Bonn
dc.publisher.locationBonn
dc.rights.accessRightsopenAccess
dc.identifier.urnhttps://nbn-resolving.org/urn:nbn:de:hbz:5n-35347
ulbbn.pubtypeErstveröffentlichung
ulbbn.birthnameSchröder
ulbbnediss.affiliation.nameRheinische Friedrich-Wilhelms-Universität Bonn
ulbbnediss.affiliation.locationBonn
ulbbnediss.thesis.levelDissertation
ulbbnediss.dissID3534
ulbbnediss.date.accepted2013-10-14
ulbbnediss.instituteMathematisch-Naturwissenschaftliche Fakultät : Fachgruppe Molekulare Biomedizin / Life & Medical Sciences-Institut (LIMES)
ulbbnediss.fakultaetMathematisch-Naturwissenschaftliche Fakultät
dc.contributor.coRefereeKolanus, Waldemar


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