Title:Acute Versus Chronic Administration of Calcineurin-Inhibitors Differentially Affect T-Cell Function
Volume: 21
Issue: 6
Author(s): Julia Kirchhof, Benjamin Wilde*, Justine Schmidt, Nils Mülling, Liubov Petrakova, Alexandra Brinkhoff, Manfred Schedlowski and Oliver Witzke
Affiliation:
- Department of Nephrology, University Hospital Essen, University of Duisburg- Essen,Germany
Keywords:
CD25, cyclosporine A, interleukin-2, renal transplantation, T-Cell, tacrolimus.
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.