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Discontinuation of calcineurin inhibitors treatment allows the development of FOXP3+ regulatory T‐cells in patients after kidney transplantation
Author(s) -
van de Wetering Jacqueline,
Koumoutsakos Periklis,
Peeters Annemiek,
van der Mast Barbara J.,
de Kuiper Petronella,
IJzermans Jan N.M.,
Weimar Willem,
Baan Carla C.
Publication year - 2011
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/j.1399-0012.2010.01311.x
Subject(s) - granzyme b , medicine , foxp3 , calcineurin , transplantation , fas ligand , il 2 receptor , immunology , perforin , endocrinology , immune system , cd8 , apoptosis , biology , t cell , biochemistry , programmed cell death
van de Wetering J, Koumoutsakos P, Peeters A, van der Mast BJ, de Kuiper P, IJzermans JNM, Weimar W, Baan CC. Discontinuation of calcineurin inhibitors treatment allows the development of FOXP3+ regulatory T‐cells in patients after kidney transplantation.
Clin Transplant 2011: 25: 40–46. © 2010 John Wiley & Sons A/S. 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 detectable and non‐detectable donor‐specific cytolysis reactivity; FOXP3 transcript values were highest in absence of donor‐specific cytotoxicity (p < 0.01). Our study shows CNI withdrawal in stable kidney transplant recipients two yr after transplantation is safe. Moreover, discontinuation of CNIs’ treatment allows FOXP3+ regulatory T‐cells development, resulting in a significant decrease of anti‐donor immune reactivity.