Editors' ChoiceImmunology

Timely Demise and Immune Control

Science's STKE  28 Feb 2006:
Vol. 2006, Issue 324, pp. tw80
DOI: 10.1126/stke.3242006tw80

Apoptosis, or programmed cell death, is a fundamental means by which the immune system regulates itself. Autoimmunity develops when components of the cell death machinery, such as the cell surface receptor Fas and its ligand, are mutated or absent. Generally, this change is considered to be due to direct defects in lymphocytes, leading to their aberrant activation and proliferation. However, Chen et al. challenge this assumption by revealing that correctly regulated cell death of another central immune cell--the dendritic cell (DC)--is also required to maintain immune control. To prevent apoptosis, a transgene encoding a caspase inhibitor was targeted to DCs in mice, resulting in the accumulation of these cells both in their resting state and in situations of antigen-priming. As a consequence, T cells in these animals became chronically activated and dysregulated, leading to telltale signs of autoimmunity.

M. Chen, Y.-H. Wang, Y. Wang, L. Huang, H. Sandoval, Y.-J. Liu, J. Wang, Dendritic cell apoptosis in the maintenance of immune tolerance. Science 311, 1160-1164 (2006). [Abstract] [Full Text]