Objectives: Dendritic cells (DCs) play a key role in regulating immune responses, especially in priming naïve T-cells. Recently, DCs have been suggested to be involved in systemic lupus erythematosus (SLE) development by activating autoreactive T-helper lymphocytes. As a consequence, we compared the activation state of human monocyte-derived DCs (MDDCs) obtained from lupus patients and normal individuals.
Methods: The MDDCs were generated in vitro from blood from healthy donors and lupus patients. Immature and mature MDDCs were analysed by flow cytometry for several cell surface molecules. In parallel, cytokine secretion was determined by ELISA before and after MDDC activation. In each experiment, lupus DCs were compared with normal DCs.
Results: Here, we show for the first time that lupus MDDCs spontaneously over-express CD86 in the absence of any DC activation signal as compared with normal MDDCs (P = 0.025). Moreover, activation-induced IL-6 secretion was increased in lupus DCs with high CD86 over-expression as compared with normal DCs (P = 0.010). Interestingly, the percentage of MDDCs in lupus preparations is negatively correlated with disease activity scores (SLEDAI; P = 0.031).
Conclusions: Lupus MDDCs are pre-activated suggesting that they might be more efficient antigen-presenting cells. This result might partly explain how the peripheral tolerance is broken in SLE.