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Twenty-nine HLA-identical LR renal transplant recipients were withdrawn from AZA or MMF.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-gamma (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-gamma 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.
Gerrits
Jeroen H
JH
Department of Internal Medicine-Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
van de Wetering
Jacqueline
J
Weimar
Willem
W
van Besouw
Nicole M
NM
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D002648:Child; D004334:Drug Administration Schedule; D005190:Family; D005260:Female; D053804:Granzymes / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011239:Prednisolone / Q000627:therapeutic use*; D012086:Reoperation; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D055815:Young Adult
D006680:HLA Antigens; D007166:Immunosuppressive Agents; D013745:Tetanus Toxoid; D016753:Interleukin-10; D011239:Prednisolone; D053804:Granzymes; D009173:Mycophenolic Acid; D001379:Azathioprine