{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Muckenhuber M"],"funding":["Vienna Science and Technology Fund (Wiener Wissenschafts-, Forschungs- und Technologiefonds)"],"pagination":["4309"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11148062"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["The efficacy of costimulation blockade with CTLA4-Ig (belatacept) in transplantation is limited due to T cell-mediated rejection, which also persists after induction with anti-thymocyte globulin (ATG). Here, we investigate why ATG fails to prevent costimulation blockade-resistant rejection and how this barrier can be overcome. ATG did not prevent graft rejection in a murine heart transplant model of CTLA4-Ig therapy and induced a pro-inflammatory cytokine environment. While ATG improved the balance between regulatory T cells (Treg) and effector T cells in the spleen, it had no such effect within cardiac allografts. Neutralizing IL-6 alleviated graft inflammation, increased intragraft Treg frequencies, and enhanced intragraft IL-10 and Th2-cytokine expression. IL-6 blockade together with AT"],"journal":["Nature communications"],"pubmed_title":["IL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice."],"pmcid":["PMC11148062"],"funding_grant_id":["LS18-031"],"pubmed_authors":["Steiner R","Kainz V","Wekerle T","Kubetz A","Weijler AM","Muckenhuber M","Regele H","Mengrelis K","Derdak S","Buresch M"],"additional_accession":[]},"is_claimable":false,"name":"IL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice.","description":"The efficacy of costimulation blockade with CTLA4-Ig (belatacept) in transplantation is limited due to T cell-mediated rejection, which also persists after induction with anti-thymocyte globulin (ATG). Here, we investigate why ATG fails to prevent costimulation blockade-resistant rejection and how this barrier can be overcome. ATG did not prevent graft rejection in a murine heart transplant model of CTLA4-Ig therapy and induced a pro-inflammatory cytokine environment. While ATG improved the balance between regulatory T cells (Treg) and effector T cells in the spleen, it had no such effect within cardiac allografts. Neutralizing IL-6 alleviated graft inflammation, increased intragraft Treg frequencies, and enhanced intragraft IL-10 and Th2-cytokine expression. IL-6 blockade together with AT","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2026-06-02T06:14:44.651Z","creation":"2026-04-15T03:14:51.59Z"},"accession":"S-EPMC11148062","cross_references":{"pubmed":["38830846"],"doi":["10.1038/s41467-024-48574-w"]}}