Defects in Antiviral T Cell Responses Inflicted by Aging-Associated miR-181a Deficiency

Chulwoo Kim, Rohit R. Jadhav, Claire E. Gustafson, Megan J. Smithey, Alec J. Hirsch, Jennifer L. Uhrlaub, William H. Hildebrand, Janko Nikolich-Žugich, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Generation of protective immunity to infections and vaccinations declines with age. Studies in healthy individuals have implicated reduced miR-181a expression in T cells as contributing to this defect. To understand the impact of miR-181a expression on antiviral responses, we examined LCMV infection in mice with miR-181ab1-deficient T cells. We found that miR-181a deficiency delays viral clearance, thereby biasing the immune response in favor of CD4 over CD8 T cells. Antigen-specific CD4 T cells in mice with miR-181a-deficient T cells expand more and have a broader TCR repertoire with preferential expansion of high-affinity T cells than in wild-type mice. Importantly, generation of antigen-specific miR-181a-deficient CD8 effector T cells is particularly impaired, resulting in lower frequencies of CD8 T cells in the liver even at time points when the infection has been cleared. Consistent with the mouse model, CD4 memory T cells in individuals infected with West Nile virus at older ages tend to be more frequent and of higher affinity. T cell aging in humans is associated with progressive loss in miR-181a, the implications of which for antiviral immunity are unknown. Using mouse models, Kim et al. find that miR-181a deficiency in T cells reproduces many aging features including impaired effector T cell expansion, viral clearance, generation of tissue-residing T cells, and recall responses.

Original languageEnglish (US)
Pages (from-to)2202-2216.e5
JournalCell Reports
Volume29
Issue number8
DOIs
StatePublished - Nov 19 2019

Keywords

  • CD8 effector T cell
  • T cell repertoire
  • antiviral response
  • immune aging
  • immunosenescence
  • microRNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Defects in Antiviral T Cell Responses Inflicted by Aging-Associated miR-181a Deficiency'. Together they form a unique fingerprint.

  • Cite this

    Kim, C., Jadhav, R. R., Gustafson, C. E., Smithey, M. J., Hirsch, A. J., Uhrlaub, J. L., Hildebrand, W. H., Nikolich-Žugich, J., Weyand, C. M., & Goronzy, J. J. (2019). Defects in Antiviral T Cell Responses Inflicted by Aging-Associated miR-181a Deficiency. Cell Reports, 29(8), 2202-2216.e5. https://doi.org/10.1016/j.celrep.2019.10.044