Dendritic cells (DC) displays the unique ability to activate naive T cells and to initiate primary T-cell responses revealed in DC – T cell alloreactions. DC frequently operate under stress conditions. Oxidative stress enhances the production of inflammatory cytokines by DC. We performed a proteomic analysis in order to see which major changes occur, at the protein expression level, during DC differentiation and maturation. Comparative 2D gel analysis of the monocyte, immature DC and mature DC stages were performed. Manganese superoxide dismutase (MnSOD), reaches 0.7% of the gel-displayed proteins at the mature DC stage. This important amount of MnSOD is a primary antioxidant defence system against superoxide radicals, but its product, H2O2, is also deleterious for cells. Peroxiredoxin enzymes (Prx) play an important role in eliminating such peroxide. Prx1 expression level continuously increases during DC differentiation and maturation while Prx6 continuously decreases and Prx2 peaks at the immature DC stage. As a consequence, DC are more resistant than monocytes to apoptosis induced by high amounts of oxidized low-density lipoproteins (oxLDL) containing toxic organic peroxides and hydrogen peroxide. Furthermore, DC-stimulated T cells produce high levels of receptor activator of nuclear factor B ligand (RANKL), a chemotactic and survival factor for moncocytes and DC. This study provides insights into the original ability of DC to express very high levels of antioxidant enzymes such as MnSOD and Prx1, to detoxify oxLDL and to induce high levels of RANKL by the T cells they activate, and further emphasizes the role that DC might play in atherosclerosis, a pathology recognized as a chronic inflammatory disorder.