A role for apoptosis-inducing factor in T cell development

被引：13

作者：

Banerjee, Hridesh ^{[1
]}

Das, Abhishek ^{[1
]}

Srivastava, Smita ^{[1
]}

Mattoo, Hamid R. ^{[1
]}

Thyagarajan, Krishnamurthy ^{[1
]}

Khalsa, Jasneet Kaur ^{[1
]}

Tanwar, Shalini ^{[1
]}

Das, Deepika Sharma ^{[1
]}

Majumdar, Subeer S. ^{[1
]}

George, Anna ^{[1
]}

Bal, Vineeta ^{[1
]}

Durdik, Jeannine M. ^{[2
]}

Rath, Satyajit ^{[1
]}

机构：

[1] Natl Inst Immunol, New Delhi 110067, India

[2] Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2012年 / 209卷 / 09期

基金：

美国国家卫生研究院;

关键词：

CHAIN GENE REARRANGEMENT; THYMIC ORGAN-CULTURES; THYMOCYTE DEVELOPMENT; FACTOR AIF; OXIDATIVE-PHOSPHORYLATION; BETA-SELECTION; IN-VIVO; RECEPTOR; DEATH; SURVIVAL;

D O I：

10.1084/jem.20110306

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Apoptosis-inducing factor (Aif) is a mitochondrial flavoprotein that regulates cell metabolism and survival in many tissues. We report that aif-hypomorphic harlequin (Hq) mice show thymic hypocellularity and a cell-autonomous thymocyte developmental block associated with apoptosis at the beta-selection stage, independent of T cell receptor beta recombination. No abnormalities are observed in the B cell lineage. Transgenes encoding wild-type or DNA-binding-deficient mutant Aif rectify the thymic defect, but a transgene encoding oxidoreductase activity-deficient mutant Aif does not. The Hq thymic block is reversed in vivo by antioxidant treatment, and Hq T but not B lineage cells show enhanced oxidative stress. Thus, Aif, a ubiquitous protein, serves a lineage-specific nonredundant antiapoptotic role in the T cell lineage by regulating reactive oxygen species during thymic beta-selection.

引用

页码：1641 / 1653

页数：13

共 46 条

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Caspase-independent apoptotic pathways in T lymphocytes:: A minireview [J].