Kihong Lim, Ankit Dahal, Xiurui Lv, Kyun-Do Kim, Blake A Evans, Herman Li, Laurie A Steiner, Minsoo Kim
After viral infections, tissue-resident memory T cells (TRM cells) are generated and reactivated rapidly upon re-exposure to previously encountered viral pathogens, providing immediate immune effector functions to limit infection at the site of viral entry. Here we found that a subset of newly recruited CCR2+ monocytes differentiated into memory-stage CCR2-tdTomato+ cells and persisted in the lung for more than 4 months after infection with the influenza virus. Selective depletion of the memory-stage CCR2-tdTomato+ cells reduced significantly the formation of lung CD8+ TRM cells and compromised secondary heterosubtypic immune protection. Memory-stage CCR2-tdTomato+ cells colocalized with lung CD8+ TRM cells and secreted galectin-1, which activated CD8+ T cells directly and enhanced transforming growth factor-β sensing. Intranasal administration of recombinant galectin-1 as an adjuvant for the influenza vaccine induced superior memory CD8+ T cell responses. Thus, the presence of a unique memory-like monocyte-derived subset provided crucial signals to establish and maintain functional CD8+ TRM cells in the lung.