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

Immunity | Dec 13, 2004

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 RIS Download

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

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Associated grants

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

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