Human Severe Combined Immunodeficiency Due to a Defect in ZAP-70, a T Cell Tyrosine Kinase
Abstract
A homozygous mutation in the kinase domain of ZAP-70, a T cell receptor-associated protein tyrosine kinase, produced a distinctive form of human severe combined immunodeficiency. Manifestations of this disorder included profound immunodeficiency, absence of peripheral CD8^+ T cells, and abundant peripheral CD4^+ T cells that were refractory to T cell receptor-mediated activation. These findings demonstrate that ZAP-70 is essential for human T cell function and suggest that CD4^+ and CD8^+ T cells depend on different intracellular signaling pathways to support their development or survival.
- Publication:
-
Science
- Pub Date:
- June 1994
- DOI:
- 10.1126/science.8202712
- Bibcode:
- 1994Sci...264.1596E