Immune Role Discovered for the Caspase-8 Enzyme

Researchers have found that the caspase-8 enzyme, which had previously been shown to help trigger apoptosis, the programmed death of cells, is also instrumental in activating key immune system cells such as T lymphocytes, B lymphocytes and natural killer cells. The research findings were published in the September 26, 2002, issue of Nature.

The discovery of the role of caspase-8 in the activation of immune cells derived from a study carried out at the National Institute of Allergy and Infectious Diseases (NIAID) (Bethesda, MD, USA) on a brother and sister suffering from a chronic immune system disorder similar to autoimmune lymphoproliferative syndrome (ALPS), which included an overabundance of lymphocytes due to lack of apoptosis, swollen lymph nodes, and an enlarged spleen.


ALPS is known to be caused by a defect in the caspase-10 gene, which produces an enzyme that works with caspase-8 to trigger apoptosis. However, genetic tests on the children showed no defects in caspase-10. Instead, a mutation was discovered in both copies of the siblings' caspase-8 genes that rendered the caspase-8 enzyme inactive. In addition to their ALPS-like symptoms, the children's T cells, B cells, and natural killer cells were not properly activated, causing severe immunodeficiency. The result was recurrent viral infections and poor response to vaccines.

"Previously, no one had ever shown that caspase-8 played this other role,” explained senior author Dr. Michael Lenardo of NIAID's Laboratory of Immunology. "Caspase-8 deficiencies might explain why some people do not respond as well as others to vaccines, or why some people's immune systems do not fight off infections as well as others. Caspase-8 may be a useful target for a new class of anti-inflammatory or immunosuppressive therapies.”




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