Granzyme B is critical for T cell receptor-induced cell death of type 2 helper T cells
Granzyme B is critical for T cell receptor-induced cell death of type 2 helper T cells
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DOI：
10.1016/j.immuni.2006.06.011
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发表时间：
2006-08-01
期刊：
影响因子：
32.4
通讯作者：
Shi, Yufang
中科院分区：
文献类型：
--
作者：
Devadas, Satish;Das, Jyoti;Shi, Yufang
虽然CD 95 L是T细胞受体（TCR）诱导的细胞死亡（TCR-ICD）在T辅助1细胞所需的，介导TCR-ICD在Th 2细胞的分子机制是未知的。我们发现死亡受体不参与Th 2细胞的TCR-ICD，因为阻断它们的同源配体对活化的Th 2细胞的凋亡没有影响。此外，我们发现，胱天蛋白酶没有积极参与TCR-ICD的Th 2细胞。然而，抑制颗粒酶B（GrB）活性可消除Th 2细胞中的TCR-ICD，但不能消除Th 1细胞中的TCR-ICD。同样地，来自GrB缺陷小鼠的Th 2细胞对TCR-ICD具有抗性，并且GrB缺陷或GrB活性的抑制因此增强Th 2细胞因子的产生。GrB缺陷小鼠表现出对过敏原诱导的哮喘的易感性增加。因此，GrB在Th 2细胞的TCR-ICD中发挥着关键作用。
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.