A role for human renal tubular epithelial cells in direct allo-recognition by CD4+ T-cells and the effect of ischemia-reperfusion

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• dc.contributor.author Eleftheriadis, Theodoros
• dc.contributor.author Pissas, Georgios
• dc.contributor.author Crespo Barrio, Marta
• dc.contributor.author Nikolaou, Evdokia
• dc.contributor.author Liakopoulos, Vassilios
• dc.contributor.author Stefanidis, Ioannis
• dc.date.accessioned 2021-06-21T07:49:50Z
• dc.date.available 2021-06-21T07:49:50Z
• dc.date.issued 2021
• dc.description.abstract Direct allorecognition is the earliest and most potent immune response against a kidney allograft. Currently, it is thought that passenger donor professional antigen-presenting cells (APCs) are responsible. Further, many studies support that graft ischemia-reperfusion injury increases the probability of acute rejection. We evaluated the possible role of primary human proximal renal tubular epithelial cells (RPTECs) in direct allorecognition by CD4+ T-cells and the effect of anoxia-reoxygenation. In cell culture, we detected that RPTECs express all the required molecules for CD4+ T-cell activation (HLA-DR, CD80, and ICAM-1). Anoxia-reoxygenation decreased HLA-DR and CD80 but increased ICAM-1. Following this, RPTECs were co-cultured with alloreactive CD4+ T-cells. In T-cells, zeta chain phosphorylation and c-Myc increased, indicating activation of T-cell receptor and co-stimulation signal transduction pathways, respectively. T-cell proliferation assessed with bromodeoxyuridine assay and with the marker Ki-67 increased. Previous culture of RPTECs under anoxia raised all the above parameters in T-cells. FOXP3 remained unaffected in all cases, signifying that proliferating T-cells were not differentiated towards a regulatory phenotype. Our results support that direct allorecognition may be mediated by RPTECs even in the absence of donor-derived professional APCs. Also, ischemia-reperfusion injury of the graft may enhance the above capacity of RPTECs, increasing the possibility of acute rejection.
• dc.format.mimetype application/pdf
• dc.identifier.citation Eleftheriadis T, Pissas G, Crespo M, Nikolaou E, Liakopoulos V, Stefanidis I. A role for human renal tubular epithelial cells in direct allo-recognition by CD4+ T-cells and the effect of ischemia-reperfusion. Int J Mol Sci. 2021;22(4):1733. DOI: 10.3390/ijms22041733
• dc.identifier.doi http://dx.doi.org/10.3390/ijms22041733
• dc.identifier.issn 1422-0067
• dc.identifier.uri http://hdl.handle.net/10230/47944
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Int J Mol Sci. 2021;22(4):1733
• dc.rights © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword CD4+ T-cells
• dc.subject.keyword Direct allorecognition
• dc.subject.keyword Ischemia-reperfusion
• dc.subject.keyword Kidney transplantation
• dc.subject.keyword Rejection
• dc.subject.keyword Renal tubular epithelial cells
• dc.title A role for human renal tubular epithelial cells in direct allo-recognition by CD4+ T-cells and the effect of ischemia-reperfusion
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion