Differing effects of rapamycin or calcineurin inhibitor on T-regulatory cells in pediatric liver and kidney transplant recipients.
In: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jg. 12 (2012-12-01), Heft 12, S. 3449-61
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Zugriff:
In a cross-sectional study, we assessed effects of calcineurin inhibitor (CNI) or rapamycin on T-regulatory (Treg) cells from children with stable liver (n = 53) or kidney (n = 9) allografts several years posttransplant. We analyzed Treg number, phenotype, suppressive function, and methylation at the Treg-specific demethylation region (TSDR) using Tregs and peripheral blood mononuclear cells. Forty-eight patients received CNI (39 as monotherapy) and 12 patients received rapamycin (9 as monotherapy). Treg numbers diminished over time on either regimen, but reached significance only with CNI (r =-0.424, p = 0.017). CNI levels inversely correlated with Treg number (r =-0.371, p = 0.026), and positively correlated with CD127+ expression by Tregs (r = 0.437, p = 0.023). Patients with CNI levels >3.6 ng/mL had weaker Treg function than those with levels <3.6 ng/mL, whereas rapamycin therapy positively correlated with Treg numbers (r = 0.628, p = 0.029) and their expression of CTLA4 (r = 0.726, p = 0.041). Overall, CTLA4 expression, TSDR demethylation and an absence of CD127 were important for Treg suppressive function. We conclude that rapamycin has beneficial effects on Treg biology, whereas long-term and high dose CNI use may impair Treg number, function and phenotype, potentially acting as a barrier to attaining host hyporesponsiveness to an allograft.
(© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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Differing effects of rapamycin or calcineurin inhibitor on T-regulatory cells in pediatric liver and kidney transplant recipients.
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Autor/in / Beteiligte Person: | Akimova, T ; Kamath, BM ; Goebel, JW ; Meyers, KE ; Rand, EB ; Hawkins, A ; Levine, MH ; Bucuvalas, JC ; Hancock, WW |
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Zeitschrift: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, Jg. 12 (2012-12-01), Heft 12, S. 3449-61 |
Veröffentlichung: | 2023- : [New York] : Elsevier ; <i>Original Publication</i>: Copenhagen : Munksgaard International Publishers, 2001-, 2012 |
Medientyp: | academicJournal |
ISSN: | 1600-6143 (electronic) |
DOI: | 10.1111/j.1600-6143.2012.04269.x |
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