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T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha

Yuanyuan Zha1, Reinhard Marks, Allen W Ho

  • 1Department of Pathology, Section of Hematology and Oncology, University of Chicago, Chicago, Illinois 60637, USA.

Nature Immunology
|October 10, 2006
PubMed

Insights

Defective Ras signaling contributes to T cell anergy. Restoring Ras activity and inhibiting diacylglycerol kinases (DGKs) reversed anergy, highlighting their roles in T cell function.

Area of Science:

  • Immunology
  • Cell signaling
  • Molecular biology

Background:

  • T cell anergy is linked to impaired GTPase Ras signaling.
  • Causal and mechanistic links between Ras activity and T cell anergy are not well established.

Purpose of the Study:

  • To investigate the causal role of Ras signaling in T cell anergy.
  • To elucidate the mechanisms underlying defective Ras activity in anergic T cells.

Main Methods:

  • Adenoviral transduction to manipulate nonproliferating T cells.
  • Assessing interleukin 2 production and mitogen-activated protein kinase signaling.
  • Analyzing diacylglycerol kinase (DGK) expression and Ras guanine nucleotide-exchange factor RasGRP1 translocation.

Main Results:

  • Active Ras restored interleukin 2 production and signaling in anergic T cells.
  • Diacylglycerol kinases (DGKs) were upregulated in anergic T cells.
  • DGK inhibition and defective RasGRP1 translocation were associated with T cell anergy.

Conclusions:

  • Excess DGK activity and impaired Ras signaling causally contribute to T cell anergy.
  • Restoring Ras activity is a potential therapeutic strategy for T cell anergy.

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