T-Cell Reactivity During Tapering of Immunosuppression to Low-Dose Monotherapy Prednisolone in HLA-Identical Living-Related Renal Transplant Recipients

Gerrits, Jeroen H.; van de Wetering, Jacqueline; Weimar, Willem; van Besouw, Nicole M.

Transplantation:
doi: 10.1097/TP.0b013e31819b3df2
Clinical and Translational Research
Abstract

Background. In many transplant centers, human leukocyte antigen (HLA)-identical living-related (LR) renal transplant recipients receive standard maintenance immunosuppression from 1 year after transplantation. We questioned whether discontinuation of azathioprine (AZA) or mycophenolate mofetil (MMF) influenced T-cell reactivity, circulating dendritic cell (DC) subsets numbers and their maturation status.

Methods. Twenty-nine HLA-identical LR renal transplant recipients were withdrawn from AZA or MMF. Thereafter, the patients received only prednisolone. T-cell reactivity was determined by interferon-γ (n=23), interleukin (IL)-10 (n=16), and granzyme B (n=10) Elispot assays. Circulating DC subset numbers and their maturation status determined by CCR2, CCR5, CCR7, and CD83 expression were measured by flow cytometry (n=12).

Results. The number of donor, third-party, and tetanus toxoid-reactive interferon-γ and granzyme-B producing cells was not affected after withdrawal of immunosuppression. Discontinuation of AZA or MMF resulted in significant increased numbers of third-party (P=0.003) and tetanus toxoid-reactive (P=0.008) IL-10 producing cells, and a trend in higher numbers of donor-reactive IL-10 producing cells (P=0.06). No effect was found on the number of circulating DC subsets, but DC was shifted toward a more mature phenotype.

Conclusions. In HLA-identical LR renal transplant recipients, therapy with AZA and MMF suppress the IL-10 production and the maturation of DC. This suggests that these immunosuppressants may hinder suppression of immune responses in general, including allogeneic responses.

Author Information

Department of Internal Medicine – Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

This study was supported by grant C02.2002 from the Dutch Kidney Foundation.

Address correspondence to: Nicole M. van Besouw, Ph.D., Department of Internal Medicine – Transplantation, Erasmus MC, University Medical Center Rotterdam, Room Ee-559, P.O. Box 2040, NL-3000 CA Rotterdam, The Netherlands.

E-mail: n.vanbesouw@erasmusmc.nl

Received 24 July 2008. Revision requested 18 August 2008.

Accepted 11 November 2008.

© 2009 Lippincott Williams & Wilkins, Inc.