Alveolar macrophages instruct CD8⁺ T cell expansion by antigen cross-presentation in lung

Lung CD8⁺ memory T cells play central roles in protective immunity to respiratory viruses, such as influenza A virus (IAV). Here, we find that alveolar macrophages (AMs) function as antigen-presenting cells that support the expansion of lung CD8⁺ memory T cells. Intranasal antigen administration to mice subcutaneously immunized with antigen results in a rapid expansion of antigen-specific CD8⁺ T cells in the lung, which is dependent on antigen cross-presentation by AMs. AMs highly express interleukin-18 (IL-18), which mediates subsequent formation of CD103⁺CD8⁺ resident memory T (T_RM) cells in the lung. In a mouse model of IAV infection, AMs are required for expansion of virus-specific CD8⁺ T cells and CD103⁺CD8⁺ T_RM cells and inhibiting virus replication in the lungs during secondary infection. These results suggest that AMs instruct a rapid expansion of antigen-specific CD8⁺ T cells in lung, which protect the host from respiratory virus infection.