Interstitial-resident memory CD8 T cells sustain frontline epithelial memory in the lung.

Populations of CD8 lung-resident memory T (T) cells persist in the interstitium and epithelium (airways) following recovery from respiratory virus infections. While it is clear that CD8 T cells in the airways are dynamically maintained via the continuous recruitment of new cells, there is a vigorous debate about whether tissue-circulating effector memory T (T) cells are the source of these newly recruited cells. Here we definitively demonstrate that CD8 T cells in the lung airways are not derived from T cells in the circulation, but are seeded continuously by T cells from the lung interstitium. This process is driven by CXCR6 that is expressed uniquely on T cells but not T cells. We further demonstrate that the lung interstitium CD8 T cell population is also maintained independently of T cells via a homeostatic proliferation mechanism. Taken together, these data show that lung memory CD8 T cells in the lung interstitium and airways are compartmentally separated from T cells and clarify the mechanisms underlying their maintenance.