Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice

Ziyin Wang; Miko Zhong; Chubicka Thomas; Ekaterina Kinnear; Tom Rice; Beth Holder; Beate Kampmann; John S Tregoning

doi:10.1038/s44298-024-00073-x

Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice

Npj Viruses. 2024 Dec 31;2(1):71. doi: 10.1038/s44298-024-00073-x. eCollection 2024 Dec.

Authors

Ziyin Wang¹, Miko Zhong¹, Chubicka Thomas¹, Ekaterina Kinnear¹, Tom Rice^{2

3}, Beth Holder², Beate Kampmann⁴, John S Tregoning¹

Affiliations

¹ Department of Infectious Disease, Imperial College London, London, SW7 2AZ UK.
² Department of Metabolism, Digestion and Reproduction, Imperial College London, London, W12 0NN UK.
³ Present Address: Centre for Endocrinology, Queen Mary University of London, London, UK.
⁴ Centre for Global Health, Charité Universitatsmedizin, Berlin, Germany.

Abstract

Maternal immunisation against respiratory viruses provides protection in early life, but as antibodies wane, there can be a gap in coverage. This immunity gap might be filled by inducing pathogen-specific lung tissue-resident T cells (TRM). However, the neonatal mouse lung has a different inflammatory environment to the adult lung which affects T cell recruitment. We compared the factors affecting viral-specific TRM recruitment in the lungs of adult or neonatal mice. In contrast to adulthood, we demonstrated that RSV or influenza infection in neonatal mice recruited fewer TRM to the lungs. This was associated with reduced lung levels of CCL5 and CXCL10. Co-administration of CCL5 or CXCL10 at the time of primary T cell activation significantly increased RSV-specific TRM in the lung, protecting mice upon reinfection. These chemokine differences were reflected in responses to infection in human cord blood. Here we show a critical role for CCL5 and CXCL10 in the induction of lung TRM and a possible strategy for boosting responses.

Keywords: Immunopathogenesis; Vaccines.