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

Takamura, Shiki

M emory T cells have been divided into two distinct subsets based on their distinct migratory properties (107) . Central memory T (T CM ) cells express lymph nodehoming receptors L-selectin (CD62L) and CC-chemokine receptor 7 (CCR7), and preferentially circulate between lymph nodes and blood. Effector memory T (T EM ) cells lack the expressions of these receptors and circulate between the blood and nonlymphoid barrier tissues such as the skin, lung, intestines, and female reproductive tract. Upon secondary infection, T EM cells exhibit immediate effector functions at the site of infection, while T CM cells undergo extensive expansion in the draining lymph nodes before migrating to the site of infection and eliminating virus-infected cells (106) . It has recently emerged that memory T cells in the nonlymphoid tissues, which had previously been classified as a circulating T EM population, include a noncirculating cell population that resides permanently within the peripheral tissues. These cells have been termed tissue-resident memory T (T RM ) cells (34) and comprise the majority of memory T cells in the nonlymphoid tissues that confer immediate protection against peripheral infection (119) . Low levels of T EM cells also transit the peripheral tissues and contribute to local protection (83) . More recent studies have revealed that T RM cells are present in wide variety of lymphoid and nonlymphoid tissues, including brain, salivary glands, thymus, spleen, lymph nodes, liver, kidneys, pancreas, heart, and dorsal root ganglia (96) . The generation and maintenance of T RM cells in each of these tissues differ significantly, indicating a major role for tissue-specific instruction (53) . Therefore, there is a need to identify the unique signals underlying each tissue microenvironment and the molecular mechanisms that instruct T RM formation.