A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion
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 probabilit...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1733 |
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| author | Theodoros Eleftheriadis Georgios Pissas Marta Crespo Evdokia Nikolaou Vassilios Liakopoulos Ioannis Stefanidis |
| author_facet | Theodoros Eleftheriadis Georgios Pissas Marta Crespo Evdokia Nikolaou Vassilios Liakopoulos Ioannis Stefanidis |
| author_sort | Theodoros Eleftheriadis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:00:51Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:00:51Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2f4348aff98b4a8e8e6657ff9fb7353e2023-12-03T12:59:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224173310.3390/ijms22041733A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-ReperfusionTheodoros Eleftheriadis0Georgios Pissas1Marta Crespo2Evdokia Nikolaou3Vassilios Liakopoulos4Ioannis Stefanidis5Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceNephrology Department, Institut Hospital del Mar d’Investigacions Mèdiques, Hospital del Mar, Parc de Salut Mar, 08003 Barcelona, SpainDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceDepartment of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, GreeceDirect 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.https://www.mdpi.com/1422-0067/22/4/1733kidney transplantationrenal tubular epithelial cellsdirect allorecognitionCD4+ T-cellsischemia-reperfusionrejection |
| spellingShingle | Theodoros Eleftheriadis Georgios Pissas Marta Crespo Evdokia Nikolaou Vassilios Liakopoulos Ioannis Stefanidis A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion International Journal of Molecular Sciences kidney transplantation renal tubular epithelial cells direct allorecognition CD4+ T-cells ischemia-reperfusion rejection |
| title | A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion |
| title_full | A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion |
| title_fullStr | A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion |
| title_full_unstemmed | A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion |
| title_short | A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion |
| title_sort | role for human renal tubular epithelial cells in direct allo recognition by cd4 t cells and the effect of ischemia reperfusion |
| topic | kidney transplantation renal tubular epithelial cells direct allorecognition CD4+ T-cells ischemia-reperfusion rejection |
| url | https://www.mdpi.com/1422-0067/22/4/1733 |
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