Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory CD8(+) T Cells

Takamura, Shiki

A revised theory on continual recruitment and permanent deposition A primary definition of T RM cells is that they are maintained in the lymphoid and nonlymphoid tissues without recirculation. This definition clearly applies to lung airway memory CD8 + T cells because, once recruited, those cells do not return to the circulation or the lung interstitium (47) . However, maintenance of this population differs significantly from that of CD8 + T RM cells in other mucosal tissues. For example, although lung airway memory CD8 + T cells are not highly apoptotic, it has demonstrated that the half-life of this population is *2 weeks (24). Such a short lifespan is likely due to the biophysical effects of the harsh airway environment: cells are being cleared by phagocytic cells or removed through mucociliary clearance. Furthermore, airway memory CD8 + T cells do not proliferate (47) . Based on these findings, a concept emerged that memory CD8 + T cells in the airways are continuously replaced by new cells recruited from the circulation as a process of memory T cell maintenance. This was confirmed by the continuous appearance of LFA-1 + cells in the airways even in the situation that memory CD8 + T cells downregulate LFA-1 within 48 h after entry into the airways (24) . Importantly, however, our recent findings have confirmed that only a limited number of cells in the lung airways are continually replaced by cells from the circulation. In brief, ratios of memory CD8 + T cells recruited from the circulation to the airways peaked at only *20% by 2 weeks after parabiotic surgery, and this ratio was maintained for up to 7 weeks (123) . Thus, while *20% of memory CD8 + T cells in the airways are new recruits, *80% are obviously segregated from blood-born memory CD8 + T cells, just like T RM cells in other mucosal tissues. This raised a question whether the latter cell population can survive for long in the harsh airway environment. We speculate that continual recruitment is also essential for *80% of memory CD8 + T cells in the airways. If this is the case, their source may be CD8 + T RM pools in the lung interstitium/parenchyma, but not memory CD8 + T cells in the circulation (Fig. 1) .