Dendritic Cells Commit T-cells to a Tolerant Phenotype in Tolerant Lung Transplant Recipients

WINNING ABSTRACT: 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-c, 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, CD4CD25 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-c 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/CD86CTLA4 axis.