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

Cell Rep. 2022 Feb 15;38(7):110363. doi: 10.1016/j.celrep.2022.110363.


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.

Keywords: autoimmunity; central tolerance; immunosenescence; thymus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • Antigens / immunology*
  • Antioxidants / pharmacology
  • Apolipoproteins B / metabolism
  • Atrophy
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Catalase / metabolism
  • Dietary Supplements
  • Immunity* / drug effects
  • Immunodominant Epitopes / immunology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Orthomyxoviridae / drug effects
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae Infections / immunology
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Self Tolerance / drug effects
  • Self Tolerance / immunology*
  • Stromal Cells / drug effects
  • Stromal Cells / enzymology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Thymus Gland / pathology


  • Antigens
  • Antioxidants
  • Apolipoproteins B
  • Immunodominant Epitopes
  • Catalase