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Publication : Granzyme B is critical for T cell receptor-induced cell death of type 2 helper T cells.

First Author  Devadas S Year  2006
Journal  Immunity Volume  25
Issue  2 Pages  237-47
PubMed ID  16901729 Mgi Jnum  J:113469
Mgi Id  MGI:3686814 Doi  10.1016/j.immuni.2006.06.011
Citation  Devadas S, et al. (2006) Granzyme B is critical for T cell receptor-induced cell death of type 2 helper T cells. Immunity 25(2):237-47
abstractText  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.
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