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

Takamura, Shiki

Influence of chemokines on the active and basal recruitment of CD8 + T cells to the lung Unlike skin and intestines, where specialized adhesion molecules and chemokine receptors regulate selective migration of T cells to those tissues (e.g., integrin a4b7 and FIG. 1. Compartmentalization of CD8 + T RM cells and CD8 + T EM cells in the lung. Memory CD8 + T cells in the lung consists of a major (*80%) population of T RM cells and a minor (*20%) population of T EM cells. During the acute phase of a respiratory virus infection, effector CD8 + T cells are recruited to the lung (active recruitment) and acquire tissuederived instructions necessary for differentiation into terminal effector cells. CD8 + T RM precursors are recruited to the site of tissue damage during later stages of the infection and receive instructive signals from several factors (such as local antigen and TGF-b) before differentiating into T RM cells. CD8 + T RM niches (RAMDs) are created as a consequence of tissue remodeling and provide temporal spaces for the maintenance of CD8 + T RM cells. CD8 + T RM cells in the RAMDs are maintained in a CD69-independent manner due to spatial separation from the lymphatics. Because CD8 + T RM cells in the lung airways are short-lived, this population may be maintained by the continual recruitment of cells from the CD8 + T RM pool in the lung interstitium/parenchyma. CD8 + T EM cells are recruited to the uninfected lung interstitium during steady state (basal recruitment). Those cells are segregated from the CD8 + T RM niches and residual antigen-presenting cells in the lung, thereby causing them to exit from this tissue through the lymph in response to S1P-induced chemotactic signal. Some cells are activated by antigen-independent stimulus in the interstitium and transiently express CD69. CD69-mediated inhibition of S1P 1 leads to temporal retention of CD8 + T EM cells in the interstitium, which potentially enable subsequent recruitment of cells to the lung airways. RAMDs, repair-associated memory depots; S1P, sphingosine 1-phosphate; T EM , effector memory T; TGF-b, transforming growth factor-b; T RM , tissue-resident memory T.