Heightened Susceptibility to Influenza Mortality in Immunodeficient Mice Caused by a T-Cell Specific Defect in SOD2. Academic Article uri icon


  • Abstract Abstract 1655 Poster Board I-681 The role of SOD2 in development and function of the immune system remains unknown. Due to the early lethality of constitutive SOD2 knock-out mice, we recently reported the creation of T-cell specific SOD2 conditional knock-out mice to identify an immunological role, if any, for MnSOD in a viable organism. Knock-out mice displayed decreases in T-cell numbers (2-5 fold) within all lymphoid organs assayed (i.e. thymus, spleen, lymph nodes, and peripheral blood). Quantitative morphometry on transmission electron micrographs of SOD2 knock-out thymocytes indicated defects in mitochondrial morphology compared to controls. Further analysis of T-cell subpopulations by flow cytometry revealed that a T-cells had the largest decrease in number (CD4-,CD8+ affected more than CD4+,CD8-), while the d T-cell population appeared unaffected or increased. The SOD2 knock-out T-cells demonstrated a more sizable activated population (CD44+, CD62L-) than the controls (2 fold for both CD4-,CD8+ and CD4+,CD8-), and mRNA expression microarray analysis showed up-regulation of numerous genes involved in T-cell activation. To query immune system function in the mice with SOD2-/- T-cells, we challenged the knock-out mice with influenza A virus (IAV). Upon infection, the knockout animals suffered from increased morbidity (i.e. weight loss) and 100% succumbed to infection within 11 days, whereas all control animals made a full recovery despite initial morbidity. Characterization of T-cell response to IAV in the knock-outs revealed limited T-cell migration to the lungs (2-fold fewer), smaller IAV-specific tetramer-positive populations, and attenuation of interferon gamma (INF) production. Taken together, these results indicate that MnSOD is critical for proper immune system development and function. Future studies will examine the mechanism of the decrease in T-cell numbers as well testing pharmaceutical SOD mimetics that may demonstrate a rescue of the observed phenotype. This work was supported by NIH grants CA73612 and CA115438. Disclosures No relevant conflicts of interest to declare.

published proceedings

  • Blood

author list (cited authors)

  • Case, A. J., Mcgill, J. L., Sangster, S. C., Madsen, J. M., Tygrett, L. T., Johns, A. G., ... Domann, F. E.

complete list of authors

  • Case, Adam John||Mcgill, Jodi L||Sangster, Stephen C||Madsen, Joshua M||Tygrett, Lorraine T||Johns, Anna G||Takahashi, Takamune||Shirasawa, Takuji||Spitz, Douglas R||Meyerholz, David K||Waldschmidt, Thomas J||Legge, Kevin L||Domann, Frederick E

publication date

  • November 2009

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