Influenza-Specific Lung-Resident Memory CD8⁺ T Cells

Despite the availability of seasonal vaccines, influenza A (IAV) prevails as a leading cause of respiratory infection worldwide. Current vaccination efforts aim at increasing protection against heterologous and potentially pandemic IAV strains. Lung-resident CD8⁺ T cells (Trm) generated upon IAV infection are vital for heterosubtypic immunity to IAV reexposure and provide quick and robust responses upon reactivation. Yet, protection wanes with time as lung Trm cell numbers decline, a contrasting feature with Trm cells at other mucosal sites such as the skin. In this review, we discuss current data on lung Trm compared to Trm cells in other tissues. Furthermore, major knowledge gaps in the generation and maintenance of IAV-specific lung Trm are addressed and mechanisms that may contribute to their decline are discussed. Further understanding in the mechanisms that govern effector function versus immunopathology is paramount for future IAV vaccine design in enhancing durability of lung Trm cells.