Journal article
Elevated mitochondrial superoxide disrupts normal T cell development, impairing adaptive immune responses to an influenza challenge
Free radical biology & medicine, Vol.50(3), pp.448-458
02/01/2011
DOI: 10.1016/j.freeradbiomed.2010.11.025
PMID: 21130157
Abstract
Reactive oxygen species (ROS) are critical in a broad spectrum of cellular processes including signaling, tumor progression, and innate immunity. The essential nature of ROS signaling in the immune systems of Drosophila and zebrafish has been demonstrated; however, the role of ROS, if any, in mammalian adaptive immune system development and function remains unknown. This work provides the first clear demonstration that thymus-specific elevation of mitochondrial superoxide (O2•−) disrupts normal T cell development and impairs the function of the mammalian adaptive immune system. To assess the effect of elevated mitochondrial superoxide in the developing thymus, we used a T-cell-specific knockout of manganese superoxide dismutase (i.e., SOD2) and have thus established a murine model to examine the role of mitochondrial superoxide in T cell development. Conditional loss of SOD2 led to increased superoxide, apoptosis, and developmental defects in the T cell population, resulting in immunodeficiency and susceptibility to the influenza A virus H1N1. This phenotype was rescued with mitochondrially targeted superoxide-scavenging drugs. These findings demonstrate that loss of regulated levels of mitochondrial superoxide lead to aberrant T cell development and function, and further suggest that manipulations of mitochondrial superoxide levels may significantly alter clinical outcomes resulting from viral infection.
Details
- Title: Subtitle
- Elevated mitochondrial superoxide disrupts normal T cell development, impairing adaptive immune responses to an influenza challenge
- Creators
- Adam J Case - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Carver College of Medicine, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USAJodi L McGill - Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USALorraine T Tygrett - Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USATakuji Shirasawa - Department of Aging Control Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-0033, JapanDouglas R Spitz - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Carver College of Medicine, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USAThomas J Waldschmidt - Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAKevin L Legge - Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USAFrederick E Domann - Free Radical and Radiation Biology Program, Department of Radiation Oncology, Carver College of Medicine, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.50(3), pp.448-458
- DOI
- 10.1016/j.freeradbiomed.2010.11.025
- PMID
- 21130157
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 02/01/2011
- Academic Unit
- Microbiology and Immunology; Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047702202771
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