Altered dendritic cells with tolerizing phenotype in patients with systemic lupus erythematosus

Earlier we showed the generation of tolerizing human monocyte-derived DC following interaction with iC3b-opsonized apoptotic cells. In this study we examine the generation of DC with our previously described tolerogenic phenotype in patients with the systemic autoimmune disease systemic lupus erythematosus (SLE). Monocyte-derived DC were generated in 71 SLE patients, characterized, and then tested for clearance of iC3b-opsonized 1,1′-dioctadecyl- 3,3,3′,3′-tetramethyl- indocarbocyanineperchlorate -stained apoptotic cells using flow cytometry, and for autologous T-cell activation using autologous mixed lymphocyte reaction (AMLR), at the same time as controls. Compared with healthy, age-and gender-matched controls, SLE patients showed upregulation of MHC class II, with a mean expression of 130.5%±36.8% (p<0.007); CD86 in immature DC from SLE patients, generated in autologous human or control plasma, were also upregulated, with mean expression 106.6%±18.0% (p<0.03). A significant (>20%) reduction in iC3b-apoptotic cell uptake, together with increased autologous mixed lymphocyte reaction, was seen in 75% of SLE patients. Mean 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl- indocarbocyanineperchlorate-stained apoptotic cell acquisition was 70.0%±24% (p<0.0001) compared with healthy controls. Altered generation of a tolerizing DC phenotype was seen in at least one third of SLE patients following interaction with iC3b-opsonized apoptotic cells. These results suggest that a substantial portion of SLE patients fail to generate DC with a tolerizing phenotype.