Granzyme B Is Critical for T Cell Receptor-Induced Cell Death of Type 2 Helper T Cells

Satish Devadas, Jyoti Das, Catherine Liu, Liying Zhang, Arthur I. Roberts, Zui Pan, Paul A A. Moore, Gobardhan Das, Yufang Shi

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Although CD95L is required for T cell receptor (TCR)-induced cell death (TCR-ICD) in T helper 1 cells, the molecular mechanisms mediating TCR-ICD in Th2 cells are unknown. We found that death receptors were not involved in TCR-ICD of Th2 cells because blocking their cognate ligands had no effect on apoptosis of activated Th2 cells. Furthermore, we showed that caspases were not actively involved in TCR-ICD of Th2 cells. However, inhibition of granzyme B (GrB) activity abolished TCR-ICD in Th2 cells but not Th1 cells. Likewise, Th2 cells derived from GrB-deficient mice were resistant to TCR-ICD, and GrB deficiency or inhibition of GrB activity consequently enhanced the production of Th2 cytokines. GrB-deficient mice exhibited increased susceptibility to allergen-induced asthma. Thus, GrB plays a critical role in the TCR-ICD of Th2 cells.

Original languageEnglish (US)
Pages (from-to)237-247
Number of pages11
JournalImmunity
Volume25
Issue number2
DOIs
StatePublished - Aug 2006

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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