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

Takamura, Shiki

It has also demonstrated that residual antigen presentation persists in the MLN for several months after acute respiratory virus infections (54, 55, 62, 75, 122, 138) . Because memory CD8 + T cells in the MLN and the lung airways exhibit similar activated phenotypes, it has been suggested that reactivation by residual antigen in the MLN induces the migration of memory CD8 + T cells from the MLN to the lung airways, resulting in the continual influx of cells to the airways (138) . In other words, reactivation in the MLN induces phonotypic changes in memory T cells from lymph node-surveying T CM to peripheral tissue homing T EM cells (122, 138) . However, it should be noted that the basal levels of continual recruitment of cells to the airways also occur in the absence of residual antigen (65) . Furthermore, memory CD8 + T cells in the circulation gradually lose the expressions of Blimp-1 and Hobit (117), key transcription factors regulating tissue retention (79) . As a result, the efficacy of continual (basal) recruitment to the airways wanes over time (117) . One should also be mindful of the fact that signature markers of T RM cells, such as CD69 and CD103, could be upregulated on lung-circulating blood-born CD8 + T EM cells in certain tissue environments (65) or basal levels of TNF secreted in the lung (117) . However, it is still unclear whether T EM -derived CD69 + CD103 + cells acquire certain tissue residency. (117, 123) Thus, a more precise analysis of migratory property is required to define CD8 + T RM cells in the lung. Nevertheless, lung-circulating CD8 + T EM cell populations should not be neglected as those populations could be majority when bona fide T RM cells disappeared (117) , and have an ability to contribute, in part, to the protective immunity upon rechallenge (116) .