颗粒酶B对于2型辅助性T细胞的T细胞受体诱导的细胞死亡至关重要。

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

作者信息

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

机构信息

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.

出版信息

Immunity. 2006 Aug;25(2):237-47. doi: 10.1016/j.immuni.2006.06.011. Epub 2006 Aug 10.

DOI:10.1016/j.immuni.2006.06.011

PMID:16901729

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.

摘要

虽然CD95L对于辅助性T细胞1（Th1）中T细胞受体（TCR）诱导的细胞死亡（TCR-ICD）是必需的，但介导Th2细胞中TCR-ICD的分子机制尚不清楚。我们发现死亡受体不参与Th2细胞的TCR-ICD，因为阻断其同源配体对活化的Th2细胞凋亡没有影响。此外，我们表明半胱天冬酶不积极参与Th2细胞的TCR-ICD。然而，颗粒酶B（GrB）活性的抑制消除了Th2细胞而非Th1细胞中的TCR-ICD。同样，来自GrB缺陷小鼠的Th2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了Th2细胞因子的产生。GrB缺陷小鼠表现出对变应原诱导的哮喘易感性增加。因此，GrB在Th2细胞的TCR-ICD中起关键作用。