Document Detail

CD154 is expressed during treatment with calcineurin inhibitors after organ transplantation.
MedLine Citation:
PMID:  12042657     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: CD154 (CD40 ligand) monoclonal antibody prevents allograft rejection in rodents and monkeys. Inasmuch as calcineurin inhibitors (CI) inhibit CD154 expression by pharmacologic agents in vitro, we investigated whether CD154 is also inhibited by CI in vivo and in vitro during allogeneic stimulation. METHODS: CD154 expression was determined by immunohistochemistry and flow cytometry in human lymph nodes and spleen sections from rhesus monkeys with or without CI treatment. The effect of CI on induction of CD154 expression was studied by stimulating lymphocytes with phorbol 12-myristate 13-acetate (PMA) and ionomycin or with allogeneic monocyte-derived mature dendritic cells. RESULTS: Lymph nodes from patients with or without CI cyclosporine (CsA) or FK506 (FK) treatment showed comparable CD154 expression, which was present on the cell surface of T cells. CD154-expressing cells were also present in spleens from monkeys treated with CsA in comparable numbers to those in the nontreated group. Moreover, in several liver transplant rejection biopsies taken during CI therapy CD154-expressing cells were observed. In vitro, CsA and FK strongly inhibited induction of CD154 expression on peripheral blood mononuclear cells by pharmacologic stimuli. Maximum inhibition was found at 50 ng/ml CsA and 20 ng/ml FK. CD154 expression induced by dendritic cells in peripheral blood mononuclear cells or spleen cells was also almost completely inhibited by CsA. CONCLUSION: Although CI strongly suppressed pharmacologic and allogeneic induction of CD154 expression on T cells in vitro at concentrations at approximately clinical trough levels, CD154 is prominently expressed during CI therapy in lymphoid tissue and (sporadically) in liver allografts. This suggests that the CD154-CD40 pathway remains functional during CI therapy, which may contribute to allograft rejections in the clinical setting.
Miranda M L van Rijen; Mark L Kuijf; Herold J Metselaar; Hugo W Tilanus; Gerda J Bouma; Roel A de Weger; Margreet Jonker; Jaap Kwekkeboom
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation     Volume:  73     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-06-03     Completed Date:  2002-06-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1666-72     Citation Subset:  IM    
Department of Gastroenterology and Hepatology, University Hospital Rotterdam, Rotterdam, The Netherlands.
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MeSH Terms
Antibodies, Monoclonal / therapeutic use
CD40 Ligand / genetics*
Calcineurin / antagonists & inhibitors*
Cyclosporine / therapeutic use
Graft Rejection / prevention & control*
Heart Transplantation / immunology
Immunosuppressive Agents / therapeutic use
Kidney Transplantation / immunology
Liver Transplantation / immunology
Lymph Nodes / immunology
Spleen / immunology
Tacrolimus / therapeutic use
Transplantation, Homologous / immunology*
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Immunosuppressive Agents; 109581-93-3/Tacrolimus; 147205-72-9/CD40 Ligand; 59865-13-3/Cyclosporine; EC

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