Details

Autor(en) / Beteiligte

• McGargill, Maureen A.
• Wen, Ben G.
• Walsh, Craig M.
• Hedrick, Stephen M.

Titel

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

Ist Teil von

• Immunity (Cambridge, Mass.), 2004-12, Vol.21 (6), p.781-791

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2004

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.