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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Acute Versus Chronic Administration of Calcineurin-Inhibitors Differentially Affect T-Cell Function

Author(s): Julia Kirchhof, Benjamin Wilde*, Justine Schmidt, Nils Mülling, Liubov Petrakova, Alexandra Brinkhoff, Manfred Schedlowski and Oliver Witzke

Volume 21 , Issue 6 , 2021

Published on: 31 August, 2020

Page: [1083 - 1089] Pages: 7

DOI: 10.2174/1871530320999200831161710

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Abstract

Background: Calcineurin-inhibitors (CNI) are used in renal transplant patients (RTX) to prevent rejection. CNI mainly suppress T-cell mediated immunity but very little is known about the impact of long-term treatment with CNI on T-cell function.

Objective: We investigated the immunological effects of long-term CNI intake in RTX patients in comparison to short-term CNI administration in healthy controls (HC).

Methods: Blood was drawn from 30 RTX patients with long-term CNI treatment. In addition, blood was sampled from HC with short-term CNI treatment (four dosages) before the first and 2 hours after the last CsA intake. T-cells were analyzed for cytokine production, proliferation, and CD25 expression.

Results: Short-term CNI reduced T-cell derived IL-2 and IFNγ as well as T-cell proliferation in HC. IFNγ was not suppressed in patients with long-term CNI treatment. IL-2 production, CD25 expression, and T-cell proliferation were enhanced in long-term CNI patients.

Conclusion: Suppression of IFNγ/IL-2 and T-cell proliferation is weaker during long-term CNI treatment in patients compared to short-term treatment in healthy subjects. Enhanced CD25 expression may lower the threshold for T-cell activation during long-term CNI treatment.

Keywords: CD25, cyclosporine A, interleukin-2, renal transplantation, T-Cell, tacrolimus.

Graphical Abstract

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