Antigen-presenting cells and lung CD8⁺ resident memory T cells coordinate local immune protection and shape responses to respiratory virus infection.

The respiratory mucosa, encompassing the lungs and nasal tissues, serves as the primary barrier against respiratory viruses. While neutralizing antibodies are effective at preventing viral entry, virus-specific CD8⁺ T cells play a vital role in eliminating infected cells and inducing an antiviral state, which curbs disease progression. Among these, CD8⁺ tissue-resident memory T (TRM) cells persist long term in the lungs, where they serve as first responders and rapidly expand upon secondary respiratory virus infection to provide local protection. The establishment and maintenance of lung CD8⁺ TRM cells require not only local cytokine signals but also antigen presentation. Specific subsets of antigen-presenting cells, such as dendritic cells, alveolar macrophages, monocytes, and endothelial cells also influence the quality and durability of CD8⁺ TRM cell responses. This review summarizes key findings on CD8⁺ T cell dynamics during respiratory viral infections, with a particular focus on CD8⁺ TRM cell formation and function. We also highlight the importance of local antigen presentation in driving TRM development and discuss how this knowledge can inform vaccine strategies aimed at eliciting robust, long-lasting mucosal immunity.