Caspase-8 Initiates T-Cell Activation

A new study has shown that the enzyme caspase-8, known to be a critical factor in the process of apoptosis or programmed cell death, is directly involved in controlling immune system response through initiation of T-cell activation. The study was published March 21, 2003, in the online edition of Genes & Development.

The current study was based on earlier findings that had linked caspase-8 mutations to immunodeficiency in humans. To learn more about caspase-8, investigators from the University of Toronto (Canada; www.utoronto.ca) genetically engineered a line of mice that produced T-cells lacking the gene for caspase-8. This type of model was necessary, as mice completely lacking caspase-8 died as embryos.

The mutant mice showed a marked decrease in the number of peripheral T-cells. These cells grown in culture showed an impaired response to activation stimuli. Moreover, caspase-8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase-8 deletion in T-cells led to immunodeficiency.

"This research has helped us better understand how caspase-8 activates the immune system response by triggering T-cells to proliferate. When caspase-8 is inhibited, the immune response is significantly decreased,” explained senior author Dr. Razqallah Hakem, assistant professor in medical biophysics at the University of Toronto.



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