• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

A deficiency in Drak2 results in a T cell hypersensitivity and an unexpected resistance to autoimmunity.

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.

Pubmed ID: 15589167

Authors

  • McGargill MA
  • Wen BG
  • Walsh CM
  • Hedrick SM

Journal

Immunity

Publication Data

December 13, 2004

Associated Grants

  • Agency: NIDDK NIH HHS, Id: 5T32DK07233
  • Agency: NIAID NIH HHS, Id: AI53091-01
  • Agency: NIAID NIH HHS, Id: R01 AI053091
  • Agency: NIAID NIH HHS, Id: R01 AI053091-01
  • Agency: NIDDK NIH HHS, Id: T32 DK007233
  • Agency: NIDDK NIH HHS, Id: T32 DK007233-28

Mesh Terms

  • Animals
  • Apoptosis
  • Autoimmunity
  • Cell Proliferation
  • Cytokines
  • Encephalomyelitis, Autoimmune, Experimental
  • Gene Expression
  • Immunologic Memory
  • Lymph Nodes
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Protein Transport
  • Protein-Serine-Threonine Kinases
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes
  • Up-Regulation