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

^* UPRES EA 3287, Faculté de Médecine, Université de la Méditerranée, Marseille, ^# IFR Jean Roche, EA 2201, Marseille, France

CORRESPONDENCE: Karine Botturi, UPRES 3287, Pathologie Respiratoire Liée à l'Environnement, Faculté de Médecine, Marseille, France

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.