| http://purl.uniprot.org/citations/28062921 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28062921 | http://www.w3.org/2000/01/rdf-schema#comment | "Aims/hypothesisAdministration of anti-CD40 ligand (CD40L) antibodies has been reported to allow long-term islet allograft survival in non-human primates without the need for exogenous immunosuppression. However, the use of anti-CD40L antibodies was associated with thromboembolic complications. Targeting downstream intracellular components shared between CD40 and other TNF family co-stimulatory molecules could bypass these complications. TNF receptor associated factor 2 (TRAF2) integrates multiple TNF receptor family signalling pathways that are critical for T cell activation and may be a central node of alloimmune responses.MethodsT cell-specific Traf2-deficient mice (Traf2TKO) were generated to define the role of TRAF2 in CD4+ T cell effector responses that mediate islet allograft rejection in vivo. In vitro allograft responses were tested using mixed lymphocyte reactions and analysis of IFN-γ and granzyme B effector molecule expression. T cell function was assessed using anti-CD3/CD28-mediated proliferation and T cell polarisation studies.ResultsTraf2TKO mice exhibited permanent survival of full MHC-mismatched pancreatic islet allografts without exogenous immunosuppression. Traf2TKO CD4+ T cells exhibited reduced proliferation, activation and acquisition of effector function following T cell receptor stimulation; however, both Traf2TKO CD4+ and CD8+ T cells exhibited impaired alloantigen-mediated proliferation and acquisition of effector function. In polarisation studies, Traf2TKO CD4+ T cells preferentially converted to a T helper (Th)2 phenotype, but exhibited impaired Th17 differentiation. Without TRAF2, thymocytes exhibited dysregulated TNF-mediated induction of c-Jun N-terminal kinase (JNK) and canonical NFκB pathways. Critically, targeting TRAF2 in T cells did not impair the acute phase of CD8-dependent viral immunity. These data highlight a specific requirement for a TRAF2-NFκB and TRAF2-JNK signalling cascade in T cell activation and effector function in rejecting islet allografts.Conclusion/interpretationTargeting TRAF2 may be useful as a therapeutic approach for immunosuppression-free islet allograft survival that avoids the thromboembolic complications associated with the use of anti-CD40L antibodies."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00125-016-4198-7"xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/author | "Saito M."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/author | "Alexander S.I."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/author | "Watson K.A."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/author | "Villanueva J.E."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/author | "La Gruta N.L."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/author | "Brink R."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/author | "Grey S.T."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/author | "Walters S.N."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/author | "Zammit N.W."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/author | "Malle E.K."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/name | "Diabetologia"xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/pages | "679-689"xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/title | "Targeted deletion of Traf2 allows immunosuppression-free islet allograft survival in mice."xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://purl.uniprot.org/core/volume | "60"xsd:string |
| http://purl.uniprot.org/citations/28062921 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28062921 |
| http://purl.uniprot.org/citations/28062921 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28062921 |
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