Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice

Anna Schmidt, Jana Fuchs, Mark Dedden, Katharina Kocher, Christine Schülein, Julian Hübner, Ana Vieira Antão, Pascal Irrgang, Friederike Oltmanns, Vera Viherlehto, Natascha Leicht, Ralf Joachim Rieker, Carol Geppert, Uwe Appelt, Sebastian Zundler, Kilian Schober, Dennis Lapuente and Matthias Tenbusch ()
Additional contact information
Anna Schmidt: Institute of Clinical and Molecular Virology
Jana Fuchs: Institute of Clinical and Molecular Virology
Mark Dedden: University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg
Katharina Kocher: Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Erlangen-Nürnberg
Christine Schülein: Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Erlangen-Nürnberg
Julian Hübner: Institute of Clinical and Molecular Virology
Ana Vieira Antão: Institute of Clinical and Molecular Virology
Pascal Irrgang: Institute of Clinical and Molecular Virology
Friederike Oltmanns: Institute of Clinical and Molecular Virology
Vera Viherlehto: Institute of Clinical and Molecular Virology
Natascha Leicht: University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg
Ralf Joachim Rieker: University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg
Carol Geppert: University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg
Uwe Appelt: Friedrich-Alexander-Universität Erlangen-Nürnberg
Sebastian Zundler: University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg
Kilian Schober: Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Erlangen-Nürnberg
Dennis Lapuente: Institute of Clinical and Molecular Virology
Matthias Tenbusch: Institute of Clinical and Molecular Virology

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Lung tissue-resident memory T cells (TRM) are critical for the local control of respiratory tract infections caused by influenza A viruses (IAV). Here we compare TRM populations induced by intranasal adenoviral vector vaccines encoding hemagglutinin and nucleoprotein (NP) with those induced by an H1N1 infection in BALB/c mice. While vaccine-induced TRM express high levels of CD103 and persist longer in the lung parenchyma, short-lived, H1N1-induced TRM have a transcriptome associated with higher cytotoxic potential and distinct transcriptional profile as shown by single-cell RNA sequencing. In both the vaccine and H1N1 groups, NP-specific CD8+ T cells expand during heterologous influenza virus infection and protect the mice from disease. Meanwhile, lung inflammation in response to an infection with unrelated respiratory syncytial virus do not influence the fate of pre-existing TRM. Our preclinical work thus confirms that inflammatory conditions in the tissue shape the phenotypic and functional characteristics of TRM to serve relevant informations for optimizing mucosal vaccines.

Date: 2025
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DOI: 10.1038/s41467-025-58931-y

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