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

Takamura, Shiki

In contrast to CCR5, CXCR3 is expressed in a large fraction of antigen-specific effector as well as memory CD8 + T cells, and plays a major role in the active recruitment of those cells to the inflamed lung (30, 77, 111) . After entry into the lung, CXCR3 ligands guide effector CD8 + T cells to the sites of infection/inflammation in the lung and accelerate effector maturation (66) . Some cells maintain the expression of CXCR3 and are preferentially recruited to the vicinity of virus-infected epithelial cells and airway lumen, while cells that receive signals from IL-12 and IL-15 downregulate CXCR3 and are retained in the peribronchioarterial area where they provide a ''second wave'' of protection (1). Interestingly, Lim et al. have demonstrated that neutrophils that infiltrated the lung during the early phase of infection (around day 4) leave long-lasting trails of CXCL12 that guide and accelerate the migration of effector CD8 + T cells to the lung airways in a CXCR4-dependent manner (76) . Thus, CXCR3 and CXCR4 cooperatively regulate the active recruitment of cells into the inflamed lung. CXCR3 also contributes to the basal recruitment of memory CD8 + T cells to the lung airways in the absence of any infection in the lung (116) . This feature may reflect, in part, the superior functionality of CXCR3 hi memory CD8 + T cells in mounting recall responses against respiratory virus infection (45) .