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

Takamura, Shiki

Ultimately, a better understanding of CD8 memory in the lung is essential for the development of safe and effective vaccines capable of generating long-lasting antigen-specific memory CD8 + T cells. Despite a great deal of progress in understanding CD8 + T cell memory in the lung and recent success in generating lung CD8 + T RM cells by vaccination (37, 133, 139) , our identification of specific niches for CD8 + T RM cells in the lung and other data raises a fundamental possibility that lung CD8 + T RM cells are by necessity short lived (e.g., several months). This is primarily due to the lack of preexisting CD8 + T RM niches in the lung and the shortlived nature of these niches. Furthermore, peribronchiolar foci fill alveolar spaces, thereby reducing the efficacy of gas exchange, indicating that a risk (tissue damage and resultant functional impairment) is unavoidable to create niches for lung CD8 + T RM cells. Thus, long-term maintenance of CD8 + T RM cells in the lung and repeated tissue damage are two sides of the same coin, and future study should be focused on the balance between protective efficacy and immune pathology when considering the vaccines that target CD8 + T RM cells in the lung.