Signals for cellular cytotoxicity

The body can kill cells in two ways; a humoral response to the target cells —antibody dependent cellular cytotoxicity — or a second, antibody-independent process —natural killer cell cytotoxicity. In 1June Journal of Clinical Investigation, Jordan Orange and colleagues from Harvard Medical School, Boston, USA, show that NF-κB essential modifier (NEMO) participates in signaling pathways leading to NK cell cytotoxicity (J Clin Invest 2002, 109:1501-1509).

Orange et al. evaluated three patients with NEMO mutations and hypohidrotic ectodermal dysplasia (a rare disorder characterized by aberrant development of hair, teeth and eccrine sweat glands) who had evidence of defective CD40 signaling. In these patients they found normal percentages of peripheral blood NK cells, but impaired NK cell cytotoxic activity. Antibody-dependent cellular cytotoxicity was intact. The cytotoxic abnormality could be partially reversed by in vitro addition of interleukin 2 (IL-2), which was also able to induce NF-κB activation. In addition, in one patient ...