Airway T cells protect against RSV infection in the absence of antibody

Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8⁺ Trm cells (CD103⁺/CD69⁺) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice. Transfer of airway CD8 cells led to reduced disease and viral load and increased interferon-γ in the airways of recipient mice, while CD4 transfer reduced tumor necrosis factor-α in the airways. Because DNA vaccines induce a systemic T-cell response, we compared vaccination with infection for the effect of memory CD8 cells generated in different compartments. Intramuscular DNA immunization induced RSV-specific CD8 T cells, but they were immunopathogenic and not protective. Notably, there was a marked difference in the induction of Trm cells; infection but not immunization induced antigen-specific Trm cells in a range of tissues. These findings demonstrate a protective role for airway CD8 against RSV and support the need for vaccines to induce antigen-specific airway cells.