HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary materials and methods Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Botturi, K. Articles by Magnan, A. Search for Related Content PubMed PubMed Citation Articles by Botturi, K. Articles by Magnan, A.

CTLA-4-mediated regulatory phenotype of T-cells in tolerant lung recipients

¹ Faculty of Medicine, UPRES-EA 3287, University of the Mediterranean, and ² IFR Jean Roche, EA 2201, Marseille, France.

CORRESPONDENCE: K. Botturi, L'Institute du Thorax, Equipe AVENIR-INSERM U915, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes Cedex 1, France. Fax: 33 240412950. E-mail: botturikarine{at}yahoo.fr

Keywords: Cytotoxic T-lymphocyte antigen-4, dendritic cells, lung transplantation, obliterative bronchiolitis, T-regulatory cells

Received: July 23, 2007
Accepted January 21, 2008

Obliterative bronchiolitis (OB) is the major cause of long-term lung allograft loss resulting from an unclear immune process occurring in the absence of the donor's immune cells. The present authors hypothesised that interactions of autologous dendritic cells (DCs) with T-cells could differ in OB patients compared with healthy lung transplant recipients (LTRs).

Monocyte-derived DCs from 14 OB and 35 non-OB LTRs were cultured with autologous T-cells. T-regulatory (T_reg) cells, co-receptors, cytokine production, DC phenotype and indoleamine 2,3-dioxygenase (IDO) expression were assessed by flow cytometry. Experiments were repeated in the presence of Pseudomonas aeruginosa or anti-co-receptor antibodies.

DCs from non-OB LTR upregulated T_reg cells, cytotoxic T-lymphocyte antigen (CTLA)-4 and interleukin (IL)-10. By contrast CD28 and inducible T-cell co-stimulator were downregulated concomitantly to IL-13 and IL-4. Compared to OB, non-OB DCs displayed an immature phenotype with lower CD80 and CD83 and higher IDO levels of expression. Stimulation by P. aeruginosa did not abolish the tolerogenic effects of DCs on non-OB T-cells. Finally, decreased T_reg cells and IL-10 production were detected when adding anti-CTLA-4 antibodies in non-OB LTR.

The present study demonstrates that dendritic cells from nonobliterative bronchiolitis lung transplant recipients induce a tolerant T-cell phenotype which is dependent on cytotoxic T-lymphocyte antigen-4 engagement.