ABSTRACT
OBJECTIVES: Systemic lupus erythematosus (SLE) is characterized by the presence of autoantibodies (autoAbs) directed against the nuclear structure. Previous studies have demonstrated that dendritic cells (DCs) can process and present self-antigens (Ags) from apoptotic cells (ACs) in lupus. However, there is no direct evidence demonstrating that ACs provide self-Ags, such as histones, to stimulate autoreactive T-cells in lupus. METHODS: AC-pulsed bone marrow-derived DCs (AC-BMDCs) were used to stimulate autoreactive T-cells in vitro and in vivo. RESULTS: In our study, we found that AC-BMDCs could induce the proliferation of CD4+ T-cells from unprimed NZB x NZW F1 (BWF1) mice, which spontaneously develop SLE, but not CD4+ T-cells, from non-autoimmune DBA-2 x NZW F1 (DWF1) mice. In addition, AC-BMDCs could induce significant proliferative responses to certain histone peptide-specific T-cells. Furthermore, these AC-BMDCs could induce a considerable anti-DNA Ab response in vivo after adoptive transfer into DWF1 mice, suggesting that AC-BMDCs can break tolerance in normal mice and initiate an autoimmune response. CONCLUSION: Our study provides a direct link between self-epitopes from ACs presented by DCs and autoreactive T-cell activation, and demonstrates that ACs are critical for the induction of autoimmunity in vivo.
