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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Authors: | Theodoros Eleftheriadis Georgios Pissas Marta Crespo Evdokia Nikolaou Vassilios Liakopoulos Ioannis Stefanidis |
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Affiliation: | 1.Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece; (G.P.); (E.N.); (V.L.); (I.S.);2.Nephrology Department, Institut Hospital del Mar d’Investigacions Mèdiques, Hospital del Mar, Parc de Salut Mar, 08003 Barcelona, Spain; |
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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. |
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Keywords: | kidney transplantation renal tubular epithelial cells direct allorecognition CD4+ T-cells ischemia-reperfusion rejection |
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