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

Takamura, Shiki

As is the case with cells in the lung airways, memory CD8 + T cells in the lung interstitium/parenchyma consist of at least two distinct memory T cell subpopulations: *80% bona fide T RM cells present in the RAMDs and *20% T EM cells present the lung interstitium (123) (Fig. 1) . In the steady state in the lung, there is a balance between basal recruitment-mediated influx and S1P-mediated efflux through the lymph that maintains the flat ratio of CD8 + T EM cells (Fig. 1) . We hypothesize that a small fraction of cells are activated by antigen-independent inflammatory stimuli, potentially due to exposure with airborne contaminants. These cells upregulate CD69 expression, causing them to transiently persist in the interstitium, and some of them are then recruited to the airways through a process of basal recruitment (Fig. 1) . The mechanisms by which CD8 + T RM cells in the RAMDs are maintained remain unclear with possibilities, including homeostatic proliferation or prolonged longevity. There is evidence that CD8 + T RM cells in the lung interstitium/ parenchyma and airways are maintained independent of homeostatic cytokine IL-15 (131) . This is consistent with the relatively lower level of expression of IL-15 receptor b on memory CD8 + T cells in the lung compared to those in the spleen (112) . Nevertheless, these findings do not exclude a possibility that other factors may drive homeostatic turnover of CD8 + T RM cells in the lung RAMDs, such as residual antigen-induced reactivation. Although numerous questions remain in this field, the discovery of specific niches in the lung interstitium/parenchyma has substantial implications in 444 TAKAMURA understanding the factors regulating the maintenance of CD8 + T RM cells in the lung.