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

Takamura, Shiki

Niches and residual antigen: factors that potentially restrict the numbers of CD8 + T RM cells maintained in the lung Following a respiratory virus infection, the number of antigen-specific CD8 + T cells in the lung peaks on day 10 and then declines dramatically as infection subsides. This is followed by the establishment of CD8 + T RM cells at around 1 month postinfection. The absolute number of CD8 + T RM cells in the lung wanes over time, which results in a decrease in the protective efficacy of these cells against secondary infection with a homologous virus (67) . For example, CD8 + T RM cell-mediated protective immunity is essentially lost at 4-6 months postinfection (135) . This contrasts with the situation in the skin where CD8 + T RM cells can persist up to 1 year (137) . The shorter lifespan of lung CD8 + T RM cells could be explained by our recent findings regarding the niche-dependent maintenance of CD8 + T RM cells in the lung (123). As described above, CD8 + T RM cells are predominantly accumulated in the RAMDs: disorganized peribronchiolar foci that are temporarily created at the site of tissue damage. In fact, peribronchiolar foci still remain in the lung at a month postinfection, despite the fact that inflammatory responses have largely abated at this time point. As tissue regeneration proceeds, the size of the RAMDs shrinks over time and tends to disappear several months postinfection. Thus, we suggest that the decrease in numbers of CD8 + T RM cells in the lung for the first couple of months simply depends on the size of the RAMDs. We also suggest that an organized lymphoid structure like iBALT persists for longer periods and low numbers of CD8 + T RM cells persist in the iBALT following disappearance of RAMDs. This hypothesis is based on the idea that lung tissues do not initially have preexisted niches in which T cells can persist. Thus, the progressive loss of temporarily created ''spaces'' significantly restricts the long-term maintenance of CD8 + T RM cells.