Autophagy plays a protective role as an anti-oxidant system in human T cells and represents a novel strategy for induction of T-cell apoptosis

Ryu Watanabe, Hiroshi Fujii, Tsuyoshi Shirai, Shinichiro Saito, Tomonori Ishii, Hideo Harigae

研究成果: Article査読

18 被引用数 (Scopus)

抄録

Autophagy is an intracellular degradation system that plays an important role in T-cell survival. However, the precise mechanism linking autophagy and cell death in primary human T cells is unclear because methods for monitoring autophagy in small numbers of primary human cells remain controversial. We established a novel method for assessing autophagy in activated human T cells using a retroviral GFP-LC3 expression system. We found that autophagy was induced after TCR stimulation and that autophagy-defective naïve CD4+ T cells were susceptible to apoptosis through the intrinsic apoptotic pathway. Enhanced apoptosis of autophagy-defective T cells resulted from accumulation of ROS due to impaired mitophagy. We also demonstrated that effector memory CD4+ T cells had lower autophagic activity than naïve CD4+ T cells, which contributed to their enhanced apoptosis due to increased ROS. Moreover, blocking autophagy increased intracellular mitochondrial volume and ROS levels in activated T cells. These results suggest a protective role of autophagy as an anti-oxidant system in activated human T cells. The combination of an autophagy blocker and a mitochondrial electron transport chain inhibitor has a synergistic effect on T-cell death, which could be a novel strategy for induction of T-cell apoptosis.

本文言語English
ページ(範囲)2508-2520
ページ数13
ジャーナルEuropean Journal of Immunology
44
8
DOI
出版ステータスPublished - 2014 8

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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