Dendritic cells commit T-cells to a tolerant phenotype in tolerant lung transplant recipients

• Main Authors: K. Botturi, Y. Lacoeuille, P. Thomas, M. Reynaud-Gaubert, A. Magnan
• Format: Article
• Language: English
• Published: European Respiratory Society 2008-04-01
• Series: European Respiratory Review
• Online Access: http://err.ersjournals.com/cgi/content/full/17/107/51
• ISSN: 0905-9180; 1600-0617

Immune characteristics distinguishing tolerant lung transplant recipients (LTR) from patients with Bronchiolitis obliterans syndrome (BOS) are largely unknown. We compared the effect of dendritic cells (DC) on T-cell activation in healthy LTR (non BOS) and in BOS patients. 30 Non BOS and 14 BOS recipients were studied. Mature dendritic cells were derived from blood monocytes and co-cultured with autologous T cells at various ratios. T cell CD69, CD25, CD28, ICOS and CTLA-4 expression and IL-4, IL-13, IFN-, and IL-10 production were assessed by flow cytometry. Dendritic cell expression of surface markers and indoleamine 2,3 dioxygenase was also studied. Experiments were repeated in presence of P. aeruginosa or anti-CTLA-4 antibodies. In dendritic cell/LT co-cultures, T cell CD69, CD28 and ICOS decreased in non BOS (p<0.03). By contrast, CD4+CD25+high T regulatory cells (Treg), CTLA4 expression and IL-10 production increased (p<0.05). Il-13 and IL-4 decreased in non BOS only (p<0.03), whereas IFN- did not vary. The increase in dendritic cell/LT ratio induced a decrease in T-cell activation in non BOS, with inverse result in BOS. Compared to BOS, dendritic cells from non BOS displayed a down-modulation of CD83, CD80 and higher levels of IDO (p<0.05). Stimulation by P. aeruginosa did not remove tolerogenic effect of dendritic cells on non BOS T-cells. Finally, decreased Treg and expression of IL-10 were detected when adding anti-CTLA-4 in non BOS (p<0.05) but not in BOS. In contrast with BOS recipients, dendritic cells from non BOS induce a tolerant T cell phenotype, by using CD80/CD86-CTLA4 axis.