Long-term maintenance of lung resident memory T cells is mediated by persistent antigen

• Published in: Mucosal immunology Vol. 14; no. 1; pp. 92 - 99
• Main Authors: Uddbäck, Ida, Cartwright, Emily K, Schøller, Amalie S, Wein, Alexander N, Hayward, Sarah L, Lobby, Jenna, Takamura, Shiki, Thomsen, Allan R, Kohlmeier, Jacob E, Christensen, Jan P
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.01.2021
• Subjects: ADNP protein; Animals; Antigens; Antigens - immunology; Antigens - metabolism; CD8 antigen; Cell differentiation; Cell-mediated immunity; Host-Pathogen Interactions; Immunization; Immunologic Memory; Immunological memory; Immunomodulation; Influenza; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Lung - immunology; Lungs; Lymphocyte Count; Lymphocytes; Lymphocytes T; Memory cells; Mice; Nucleocapsid Proteins - immunology; Parabiosis; Respiratory diseases; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Vaccines
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/s41385-020-0309-3

Tissue-resident memory T cells (T ) in the lungs are pivotal for protection against repeated infection with respiratory viruses. However, the gradual loss of these cells over time and the associated decline in clinical protection represent a serious limit in the development of efficient T cell based vaccines against respiratory pathogens. Here, using an adenovirus expressing influenza nucleoprotein (AdNP), we show that CD8 T in the lungs can be maintained for at least 1 year post vaccination. Our results reveal that lung T continued to proliferate in situ 8 months after AdNP vaccination. Importantly, this required airway vaccination and antigen persistence in the lung, as non-respiratory routes of vaccination failed to support long-term lung T maintenance. In addition, parabiosis experiments show that in AdNP vaccinated mice, the lung T pool is also sustained by continual replenishment from circulating memory CD8 T cells that differentiate into lung T , a phenomenon not observed in influenza-infected parabiont partners. Concluding, these results demonstrate key requirements for long-lived cellular immunity to influenza virus, knowledge that could be utilized in future vaccine design.