Targeted Cleavage of Signaling Proteins by Caspase 3 Inhibits T Cell Receptor Signaling in Anergic T Cells

Irene Puga, Anjana Rao, Fernando Macian

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

T cell receptor (TCR) engagement in the absence of costimulation induces the calcium-dependent upregulation of a program of gene expression that leads to the establishment of T cell anergy. Casp3 is one of the genes activated during anergy induction. Here we show that caspase 3 is required for the induction of T cell unresponsiveness. Suboptimal T cell stimulation induced caspase 3 activation, which did not result in cell death. Furthermore, caspase 3-deficient T cells showed impaired responses to anergizing stimuli. In anergic T cells, activated caspase 3 associated to the plasma membrane, where it cleaved and inactivated proteins such as the Grb2-related adaptor downstream of shc (GADS) and the guanine-nucleotide exchange factor Vav1, causing a blockade in TCR signaling. Our results identify a role for caspase 3 in nonapoptotic T cells and support that caspase 3-dependent proteolytic inactivation of signaling proteins is essential to maintain T cell tolerance.

Original languageEnglish (US)
Pages (from-to)193-204
Number of pages12
JournalImmunity
Volume29
Issue number2
DOIs
Publication statusPublished - Aug 15 2008

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Keywords

  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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