Aurora A controls CD8 + T cell cytotoxic activity and antiviral response

Sci Rep. 2019 Feb 18;9(1):2211. doi: 10.1038/s41598-019-38647-y.

Abstract

Aurora A is a serine/threonine kinase whose role in cell cycle progression and tumour generation has been widely studied. Recent work has revealed an unexpected function for Aurora A during CD4+ T cell activation and, also, in graft versus host disease development. However, it remains unknown whether Aurora A is involved in CD8+ T cell effector function and in cytotoxic T lymphocyte-mediated antiviral response. Here, we show that Aurora A chemical inhibition leads to an impairment of both the peptide-specific cytotoxicity and the degranulation activity of CD8+ T cells. This finding was similarly proven for both mice and human CD8+ CTL activity. As a result of Aurora A blockade, we detected a reduction in the expression induced by T cell activation of genes classically related to the effector function of cytotoxic T lymphocytes such as granzyme B or perforin1. Finally, we have found that Aurora A is necessary for CD8+ T cell-mediated antiviral response, in an in vivo model of vaccinia virus infection. Thus, we can conclude that Aurora A activity is, indeed, needed for the proper effector function of cytotoxic T lymphocytes and for their activity against viral threats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase A / antagonists & inhibitors
  • Aurora Kinase A / genetics*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cytotoxicity, Immunologic / genetics*
  • Disease Models, Animal
  • Host-Pathogen Interactions / genetics*
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immunomodulation / genetics
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • Vaccinia / genetics
  • Vaccinia / immunology
  • Vaccinia / virology
  • Vaccinia virus / immunology
  • Virus Diseases / genetics*
  • Virus Diseases / immunology*
  • Virus Diseases / virology

Substances

  • Receptors, Antigen, T-Cell
  • AURKA protein, human
  • Aurora Kinase A