|Title:||Dendritic Cells Pulsed with Apoptotic Cells Activate Self-Reactive T- Cells of Lupus Mice Both in Vitro and in Vivo||Authors:||SUEN, JAU-LING
|Keywords:||Apoptosis;Autoantigens;CD4þ T-cell;Dendritic cell;SL||Issue Date:||2006||Journal Volume:||v.45||Journal Issue:||n.10||Start page/Pages:||1230-1237||Source:||RHEUMATOLOGY||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.
|Appears in Collections:||醫學系|
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