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 (TRM) 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+ TRM 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.