Dendritic Cell-Based Graft Tolerance

It has recently been demonstrated that mouse and human dendritic cells (DCs) can produce IL-2 after activation. However the role of the IL2/IL2R pathway in DC functions has not yet been fully elucidated. The results presented in this study provide several new insights into the role of this pathway in DCs. We report that stimulation of human monocyte-derived DCs with LPS strongly upregulated CD25 (α chain of the IL2R) expression. In additon, by using a humanized monoclonal antibody against CD25, we demonstrated that the IL2 signalling in DC upregulated both IL-12 and γIFN production but decreased IL10 synthesis. We also found that LPS-matured DCs produced IL2. Taken together, these results suggest that IL-2 actively contributes to the DC activation through an autocrine pathway. Furthermore, our results indicate that the IL2 pathway in DC is involved in the development of T-helper priming ability and in the upregulation of surface markers characteristic of a “mature” phenotype. This study therefore provide new molecular clues regarding the split between these two phenomena and unravel new mechanisms of action of anti-CD25 monoclonal antibodies that may contribute to their action in several human immunological disorders such as autoimmune diseases and acute allograft rejection.