PMID- 19300195
OWN - NLM
STAT- MEDLINE
DCOM- 20090514
LR  - 20211203
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 87
IP  - 6
DP  - 2009 Mar 27
TI  - T-cell reactivity during tapering of immunosuppression to low-dose monotherapy 
      prednisolone in HLA-identical living-related renal transplant recipients.
PG  - 907-14
LID - 10.1097/TP.0b013e31819b3df2 [doi]
AB  - 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      recipients were withdrawn from AZA or MMF.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.
FAU - Gerrits, Jeroen H
AU  - Gerrits JH
AD  - Department of Internal Medicine-Transplantation, Erasmus MC, University Medical 
      Center Rotterdam, Rotterdam, The Netherlands.
FAU - van de Wetering, Jacqueline
AU  - van de Wetering J
FAU - Weimar, Willem
AU  - Weimar W
FAU - van Besouw, Nicole M
AU  - van Besouw NM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (HLA Antigens)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Tetanus Toxoid)
RN  - 130068-27-8 (Interleukin-10)
RN  - 9PHQ9Y1OLM (Prednisolone)
RN  - EC 3.4.21.- (Granzymes)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adult
MH  - Azathioprine/therapeutic use
MH  - Child
MH  - Drug Administration Schedule
MH  - Family
MH  - Female
MH  - Granzymes/immunology
MH  - HLA Antigens/analysis/*immunology
MH  - Humans
MH  - Immunosuppression Therapy/methods
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Interleukin-10/immunology
MH  - Kidney Transplantation/*immunology
MH  - *Living Donors
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/analogs & derivatives/therapeutic use
MH  - Prednisolone/*therapeutic use
MH  - Reoperation
MH  - T-Lymphocytes/*immunology
MH  - Tetanus Toxoid/immunology
MH  - Young Adult
EDAT- 2009/03/21 09:00
MHDA- 2009/05/15 09:00
CRDT- 2009/03/21 09:00
PHST- 2009/03/21 09:00 [entrez]
PHST- 2009/03/21 09:00 [pubmed]
PHST- 2009/05/15 09:00 [medline]
AID - 00007890-200903270-00018 [pii]
AID - 10.1097/TP.0b013e31819b3df2 [doi]
PST - ppublish
SO  - Transplantation. 2009 Mar 27;87(6):907-14. doi: 10.1097/TP.0b013e31819b3df2.