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.

Abstract:

: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.

journal_name

Eur J Immunol

authors

Watanabe R,Fujii H,Shirai T,Saito S,Ishii T,Harigae H

doi

10.1002/eji.201344248

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

2508-20

issue

8

eissn

0014-2980

issn

1521-4141

journal_volume

44

pub_type

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