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Rheumatology Advance Access published online on April 4, 2006
Rheumatology, doi:10.1093/rheumatology/kel106
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received December 7, 2005
Accepted February 24, 2006

Original Papers

Dendritic cells pulsed with apoptotic cells activate self-reactive T-cells of lupus mice both in vitro and in vivo

T.-C. Tzeng 1, J.-L. Suen 2, and B.-L. Chiang 3 *

1 Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taiwan, Republic of China
2 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China
3 Department of Pediatrics, College of Medicine, National Taiwan University, Taiwan, Republic of China

* To whom correspondence should be addressed.
B.-L. Chiang, E-mail: gicmbor{at}ha.mc.ntu.edu.tw


  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.

Keywords: Apoptosis; Autoantigens; CD4+ T-cell; Dendritic cell; SLE..
The first two authors contributed equally to this work.
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