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

Takamura, Shiki

During primary respiratory virus infections, antigenspecific CD8 + T cells are crucial to the elimination of virusinfected cells and in the case of influenza viruses, cross reactive CD8 + T cell-mediated immunity can provide protection against different viral strains (heterosubtypic immunity) (21) . Thus, understanding the mechanisms by which CD8 + T RM cells are established in the lung has important implications for vaccine development. Following resolution of respiratory virus infections, CD8 + T RM cells persist in at least two distinct compartments of the lung: the lung interstitium/parenchyma and the lung airways (44) . CD8 + T RM cells in the lung interstitium/parenchyma are mainly found as confluent peribronchiolar cell infiltrates in the interstitium and alveolar spaces (123) . Note that the term ''lung parenchyma'' indicates a part of lung involved in gas exchange, such as the alveoli, alveolar ducts, and respiratory bronchioles, but does not include the lung interstitium. In contrast, CD8 + T RM cells in the lung airways are localized primarily in the epithelial layers of the upper respiratory tract and can be easily isolated by bronchoalveolar lavage (BAL) (25, 47, 48) . Both T RM populations confer rapid protection against secondary infection (37, 91, 135) , and the number of antigen-specific CD8 + T RM cells in those tissues correlates with the efficacy of protection. Importantly, however, the molecular and cellular mechanisms underlying their recruitment, differentiation, maintenance, and recall differ significantly (44) . Thus, the precise discrimination of those populations is necessary to comprehensively understand CD8 + T cell-mediated antiviral immunity in the lung.