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Science 311 (5764): 1160-1164

Copyright © 2006 by the American Association for the Advancement of Science

Dendritic Cell Apoptosis in the Maintenance of Immune Tolerance

Min Chen,1* Yui-Hsi Wang,2 Yihong Wang,2 Li Huang,1 Hector Sandoval,1 Yong-Jun Liu,2 Jin Wang1*

Abstract: Apoptosis in the immune system is critical for maintaining self-tolerance and preventing autoimmunity. Nevertheless, inhibiting apoptosis in lymphocytes is not alone sufficient to break self-tolerance, suggesting the involvement of other cell types. We investigated whether apoptosis in dendritic cells (DCs) helps regulate self-tolerance by generating transgenic mice expressing the baculoviral caspase inhibitor, p35, in DCs (DC-p35). DC-p35 mice displayed defective DC apoptosis, resulting in their accumulation and, in turn, chronic lymphocyte activation and systemic autoimmune manifestations. The observation that a defect in DC apoptosis can independently lead to autoimmunity is consistent with a central role for these cells in maintaining immune self-tolerance.

1 Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
2 Department of Immunology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.

* To whom correspondence should be addressed. E-mail: jinwang{at}bcm.edu (J.W.); minc{at}bcm.edu (M.C.)


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