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

Takamura, Shiki

It is well known that sphingosine 1-phosphate (S1P) plays a key role in the egress of lymphocytes from the lymph nodes and thymus (4, 86) , and recent studies indicate that this is also the case for the nonlymphoid tissues (71, 78, 115, 123) . S1P is present at high levels in the blood and lymph, which results in the continuous downregulation of its receptor S1P receptor-1 (S1P 1 ) on circulating T cells (102, 110) . Upon tissue entry, CD8 + T cells instantly recover surface expression of S1P 1 due to the relatively low concentration of S1P in the parenchymal tissues (15) and are thereby subjected to opposite chemotaxis toward the lymphatics (78, 115) . Hence, a balance between the S1P-mediated exit signal and the chemokine-mediated migratory signals controls the direction of T cell migration, which potentially reflects the differential dynamics between T EM and T RM cells within the peripheral tissues.