Redox regulation of age-associated defects in generation and maintenance of T cell self-tolerance and immunity to foreign antigens

Allison K. Hester, Manpreet K. Semwal, Sergio Cepeda, Yangming Xiao, Meghan Rueda, Kymberly Wimberly, Thomas Venables, Thamotharampillai Dileepan, Ellen Kraig, Ann V. Griffith

Research output: Contribution to journalArticlepeer-review

Abstract

Thymic atrophy reduces naive T cell production and contributes to increased susceptibility to viral infection with age. Expression of tissue-restricted antigen (TRA) genes also declines with age and has been thought to increase autoimmune disease susceptibility. We find that diminished expression of a model TRA gene in aged thymic stromal cells correlates with impaired clonal deletion of cognate T cells recognizing an autoantigen involved in atherosclerosis. Clonal deletion in the polyclonal thymocyte population is also perturbed. Distinct age-associated defects in the generation of antigen-specific T cells include a conspicuous decline in generation of T cells recognizing an immunodominant influenza epitope. Increased catalase activity delays thymic atrophy, and here, we show that it mitigates declining production of influenza-specific T cells and their frequency in lung after infection, but does not reverse declines in TRA expression or efficient negative selection. These results reveal important considerations for strategies to restore thymic function.

Original languageEnglish (US)
Article number110363
JournalCell Reports
Volume38
Issue number7
DOIs
StatePublished - Feb 15 2022

Keywords

  • autoimmunity
  • central tolerance
  • immunosenescence
  • thymus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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