Elevated mitochondrial superoxide disrupts normal T cell development, impairing adaptive immune responses to an influenza challenge. Academic Article uri icon


  • 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 (O(2)(-)) 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.

published proceedings

  • Free Radic Biol Med

altmetric score

  • 2.35

author list (cited authors)

  • Case, A. J., McGill, J. L., Tygrett, L. T., Shirasawa, T., Spitz, D. R., Waldschmidt, T. J., Legge, K. L., & Domann, F. E.

citation count

  • 81

complete list of authors

  • Case, Adam J||McGill, Jodi L||Tygrett, Lorraine T||Shirasawa, Takuji||Spitz, Douglas R||Waldschmidt, Thomas J||Legge, Kevin L||Domann, Frederick E

publication date

  • February 2011