Granzyme B Is Critical for T-Cell Receptor Activation Induced Cell Death of Type 2 Helper T Cells (87.34)

Abstract

Abstract Although CD95L is required for T cell receptor activation induced cell death (AICD) in T helper 1 (Th1) cells, the molecular mechanisms mediating AICD in Th2 cells are unknown. We found that death receptor medicated apoptosis was not involved in AICD of Th2 cells because blocking their cognate ligands with recombinant soluble receptors of specific antibodies had no effect on apoptosis of activated Th2 cells. Furthermore, we showed that the major caspases were not actively involved in AICD of Th2 cells. However, inhibition of granzyme B (Gzmb) specifically abolished AICD in Th2 cells but not Th1 cells. Likewise, Th2 cells derived from Gzmb-deficient mice were resistant to AICD, and Gzmb deficiency or inhibition of Gzmb activity consequently enhanced the production of Th2 cytokines. Most interestingly, Gzmb-deficient mice exhibited increased susceptibility to allergen-induced asthma. Thus, Gzmb plays a critical role in the AICD of Th2 cells. This finding provides a novel mechanism for the balance between Th1 and Th2 cells during immune responses.