Document Detail


The impact of the CTLA-4/CD28 axis on the processes of Joint Inflammation in Rheumatoid Arthritis.
MedLine Citation:
PMID:  23045162     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: The importance of the co-stimulatory molecules CD28 and CTLA-4 in the pathological mechanism of Rheumatoid Arthritis (RA) is well documented by genetic associations and the successful clinical application of CTLA-4Ig for the treatment of RA. Here we have investigated the role of the CD28/CTLA-4 axis for the local application of CTLA-4Ig in the synovial fluid (SF) of RA patients. METHODS: We analyzed the expression of pro- and anti-inflammatory cytokines by qPCR in FACS-sorted CTLA-4 positive and negative T helper cells from peripheral blood and SF from RA patients ex vivo as well as in T helper cells in vitro after blockade of CTLA-4 by anti-CTLA-4-Fab-fragments or the blockade of B7 (CD80/CD86)-molecules by CTLA-4Ig. RESULTS: CTLA-4(+) T helper cells were unambiguously present in the SF of all RA patients examined and these expressed increased amounts of IFNγ, IL-17 but also IL-10. Furthermore, the selective blockade of CTLA-4 in T helper cells from the SF in vitro led to increased levels of IFNγ, IL-2 and IL-17. In contrast, the concomitant blockade of CD28 and CTLA-4 in T helper cells from SF of RA patients by CTLA-4Ig in vitro resulted in the reduction of the pro-inflammatory cytokines IFNγ and IL-2 accompanied by increased amounts of the anti-inflammatory cytokines IL-10 and TGFβ. CONCLUSION: Our ex vivo and in vitro results demonstrate that the CD28/CTLA-4 axis constitutes a drug target not only for the systemic but potentially also for the local application of the co-stimulation blocking agent CTLA-4Ig for the treatment of RA. © 2012 American College of Rheumatology.
Authors:
Dezsö Körmendy; Holger Hoff; Paula Hoff; Barbara M Bröker; Gerd-Rüdiger Burmester; Monika C Brunner-Weinzierl
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-8
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  -     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 by the American College of Rheumatology.
Affiliation:
Department of Rheumatology and Clinical Immunology, Charit?- University Medicine Berlin, 10117 Berlin; Deutsches Rheuma-Forschungszentrum Berlin, 10117 Berlin, Germany.
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