Browsing by Subject "Immunosuppression"
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- PublicationEmbargoIdentification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients(Oxford University Press, 2020-10-29) Boix, F.; Legaz Pérez, Isabel; Alfaro, R.; Jiménez Coll, Victor; Mrowirc, A.; Martínez Banaclocha, Helios; Galián, José Antonio; Botella, Carmen; Moya Quiles, María Rosa; Sánchez Bueno, F.; Robles, R.; Peña Moral, J. de la; Ramírez, P.; Pons, J.A.; Minguela, Alfredo; Muro, Manuel; Minhas, A.; Ciencias SociosanitariasDecreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+CD154+ and CD8+CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient–donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+CD154+ T cells (P = 0·001) and a low percentage of CD8+CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+CD154+ (P = 0·001) and CD8+CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+CD154+, CD8+CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+CD154+ and CD8+CD154+ T cells in parallel with other transplant factors.
- PublicationOpen AccessTGF-β links glycolysis and immunosuppression in glioblastoma(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Gong, Lingli; Ji, Li; Xu, Daxing; Wang, Jingjing; Zou, JianGlioblastoma (GBM) is the most common and aggressive brain tumor in adults, characterized by diffuse infiltration, dysplasia, and resistance to therapy. Metabolic remodeling and immunosuppression are typical events which contribute to GBM progression, but the molecular link between these two events remains largely undetermined. Studies have shown that high levels of transforming growth factor-β (TGF-β) and its receptors are associated with glioma malignancy and a poor prognosis. TGF-β plays an important role in cell metabolism and immunity. During tumorigenesis, TGFβ induces a shift in cell metabolism from oxidative phosphorylation to aerobic glycolysis, providing a favorable environment for tumor growth. Locally, TGFβ creates an immunosuppressive microenvironment and promotes the malignant phenotype of GBM. In this review, we aim to link GBM aerobic glycolysis and immunosuppression through TGF-β to provide new ideas for the study of GBM.
- PublicationOpen AccessThe effect of immunosuppressive therapy on renal cell apoptosis in native rat kidneys(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Kędzierska, Karolina; Sporniak-Tutak, Katarzyna; Kolasa, Agnieszka; Domański, Leszek; Domański, Maciej; Sindrewicz, Krzysztof; Smektała, Tomasz; Bober, Joanna; Safranow, Krzysztof; Osękowska, Bogumiła; Kabat-Koperska, Joanna; Baranowska-Bosiacka, Irena; Parafiniuk, Mirosław; Urasińska, Elżbieta; Ciechanowski, KazimierzAim: To analyse the impact of the most commonly used immunosuppressive drugs on the occurrence of apoptosis in the native kidneys of Wistar rats. Method: The study involved 36 rats. The animals grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The medication dose was adjusted based on available literature data. No drugs were administered to the control group. The rats were then killed. Autopsies of all animals were performed and the kidneys were isolated for histopathology (HE + PAS). To assess cell apoptosis the TUNEL reaction was performed. Blood trough levels of immunosuppressive drugs as well as the parameters of peripheral blood were determined. Results: 1. In rats treated with cyclosporine A distal nephron tubules were characterised by more pronounced apoptosis. 2. In tacrolimus-treated rats a lower intensity of apoptosis was found in the distal tubules. 3. In rapamycin-treated rats the apoptosis was inhibited both in the distal and proximal nephron tubules. 4. In MMF treated rats intense apoptosis was observed in the proximal nephron tubules. 5. There were no significant changes in renal histopathology (HE + PAS). Conclusions: The apoptosis in nephron tubules caused by immunosuppressive therapy is not accompanied by any histopathological changes (eg fibrosis, inflammation, tubular atrophy, vacuolation of the tubular cells) in light microscopy