AUTHOR=Takamura Shiki , Kohlmeier Jacob E. TITLE=Establishment and Maintenance of Conventional and Circulation-Driven Lung-Resident Memory CD8+ T Cells Following Respiratory Virus Infections JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00733 DOI=10.3389/fimmu.2019.00733 ISSN=1664-3224 ABSTRACT=

Antigen-specific CD8⁺ tissue-resident memory T cells (T_RM cells) persist in the lung following resolution of a respiratory virus infection and provide first-line defense against reinfection. In contrast to other memory T cell populations, such as central memory T cells that circulate between lymph and blood, and effector memory T cells (T_EM cells) that circulate between blood and peripheral tissues, T_RM cells are best defined by their permanent residency in the tissues and their independence from circulatory T cell populations. Consistent with this, we recently demonstrated that CD8⁺ T_RM cells primarily reside within specific niches in the lung (Repair-Associated Memory Depots; RAMD) that normally exclude CD8⁺ T_EM cells. However, it has also been reported that circulating CD8⁺ T_EM cells continuously convert into CD8⁺ T_RM cells in the lung interstitium, helping to sustain T_RM numbers. The relative contributions of these two mechanisms of CD8⁺ T_RM cells maintenance in the lung has been the source of vigorous debate. Here we propose a model in which the majority of CD8⁺ T_RM cells are maintained within RAMD (conventional T_RM) whereas a small fraction of T_RM are derived from circulating CD8⁺ T_EM cells and maintained in the interstitium. The numbers of both types of T_RM cells wane over time due to declines in both RAMD availability and the overall number of T_EM in the circulation. This model is consistent with most published reports and has important implications for the development of vaccines designed to elicit protective T cell memory in the lung.