Discontinuation of calcineurin inhibitors treatment allows the development of FOXP3+ regulatory T-cells in patients after kidney transplantation

Clinical Transplantation
Jacqueline van de WeteringCarla C Baan

Abstract

This study investigated specific gene expression profiles in patients with donor-specific cytotoxic-hyporesponsiveness, reflected by cytotoxic T-lymphocyte precursor frequency (CTLpf). The effect of calcineurin inhibitor (CNI) withdrawal was studied on markers for cytotoxicity (perforin, granzyme B), apoptosis (Fas,FasL), Th1 and Th2 cytokines (IL-2, IL-10), Th1 and Th2 transcription factors (T-bet, GATA 3), Th17 transcription factor and cytokine (RORγt, IL-17), and for immune regulation/activation (CD25, FOXP3). Peripheral blood samples from renal allograft recipients (n = 18) more than two yr after transplantation with stable renal function were analyzed before and four months after CNI withdrawal. Additionally, systolic and diastolic blood pressure, cholesterol, serum creatinine and proteinuria were evaluated, and no significant differences were measured before and after CNI withdrawal. However, CNIs' discontinuation influenced peripheral gene expression profiles. After CNI withdrawal, the mRNA expression of Granzyme B, Perforin, Fas, FasL, T-bet, GATA3 and CD25 were significantly lower than during CNI treatment. After CNI discontinuation, donor-specific CTLpf decreased, while FOXP3 expression discriminated between detectabl...Continue Reading

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Citations

Aug 28, 2012·Cellular & Molecular Immunology·Xin ZhangQuan-Xing Wang
Mar 5, 2015·Kidney International·James A Hutchinson, Edward K Geissler
Feb 28, 2013·Pediatric Transplantation·Michael M KaabakAlan K Zokoev
Apr 15, 2011·Immunological Reviews·Maria-Grazia RoncaroloRosa Bacchetta
Dec 3, 2014·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Anna Gronert ÁlvarezHeiner Wedemeyer
Nov 15, 2017·Hypertension·Valorie L ChiassonBrett M Mitchell

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