A Deficiency in Drak2 Results in a T Cell Hypersensitivity and an Unexpected Resistance to Autoimmunity

Division of Biological Sciences, Department of Cellular and Molecular Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093 USA.
Immunity (Impact Factor: 19.75). 01/2005; 21(6):781-91. DOI: 10.1016/j.immuni.2004.10.008
Source: PubMed

ABSTRACT DRAK2 is a member of the death-associated protein (DAP)-like family of serine/threonine kinases. Members of this family induce apoptosis in various cell types. DRAK2, in particular, is specifically expressed in T cells and B cells, and it is differentially regulated during T cell development. To determine whether DRAK2 regulates lymphocyte apoptosis, we produced Drak2(-/-) mice. Contrary to our expectations, Drak2(-/-) T cells did not demonstrate any defects in apoptosis or negative selection; however, T cells from Drak2(-/-) mice exhibited enhanced sensitivity to T cell receptor-mediated stimulation with a reduced requirement for costimulation. These results provide evidence that DRAK2 raises the threshold for T cell activation by negatively regulating signals through the TCR. In contrast to other models of T cell hypersensitivity, Drak2(-/-) mice were remarkably resistant to experimental autoimmune encephalomyelitis (EAE). These results expose a new pathway regulating T cell activation and highlight the intricacies of induced autoimmune disease.

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