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

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

Author information

1
Servicio de Inmunología, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
2
Department of Immunology, Ophthalmology and ENT. Complutense University School of Medicine and 12 de Octubre Health Research Institute (imas12), Madrid, Spain.
3
Cell Division and Cancer group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
4
Servicio de Inmunología, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain. fsmadrid@salud.madrid.org.
5
Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain. fsmadrid@salud.madrid.org.
6
CIBERCV, Madrid, Spain. fsmadrid@salud.madrid.org.

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.

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