Granzyme B is critical for T cell receptor-induced cell death of type 2 helper T cells.
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.
Devadas
Satish
S
Department of Molecular Genetics, Microbiology, and Immunology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.
Das
Jyoti
J
Liu
Catherine
C
Zhang
Liying
L
Roberts
Arthur I
AI
Pan
Zui
Z
Moore
Paul A
PA
Das
Gobardhan
G
Shi
Yufang
Y
D000485:Allergens / Q000276:immunology; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D005260:Female; D053804:Granzymes; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000485:Allergens; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; D020169:Caspases