T-cell reactivity during tapering of immunosuppression to low-dose monotherapy prednisolone in HLA-identical living-related renal transplant recipients
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 METHODS.: Twenty-nine HLA-identical LR renal transplant recipients were withdrawn from AZA or MMF.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.
|Keywords||Dendritic cells, HLA antigen, Immunosuppression, Minor histocompatibility antigens, Renal transplantation, T lymphocyte, T-cell reactivity, adult, article, azathioprine, child, drug administration, drug derivative, family, female, granzyme, human, immunology, immunosuppressive agent, immunosuppressive treatment, interleukin 10, kidney transplantation, living donor, male, methodology, middle aged, mycophenolic acid, mycophenolic acid 2 morpholinoethyl ester, prednisolone, reoperation, tetanus toxoid|
|Persistent URL||dx.doi.org/10.1097/TP.0b013e31819b3df2, hdl.handle.net/1765/16456|
Gerrits, J.H, van de Wetering, J, Weimar, W, & van Besouw, N.M. (2009). T-cell reactivity during tapering of immunosuppression to low-dose monotherapy prednisolone in HLA-identical living-related renal transplant recipients. Transplantation, 87(6), 907–914. doi:10.1097/TP.0b013e31819b3df2