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

从呼吸道病毒感染中恢复后，CD8 ⁺肺部驻留记忆T（T _RM）细胞的种群持续存在于间质和上皮（气道）中。尽管很明显，通过持续募集新细胞可以动态维持气道中的CD8 ⁺ T _RM细胞，但关于组织循环效应记忆T（T _EM）细胞是否是这些新募集的细胞的来源仍存在激烈的争论。在这里，我们明确证明，肺气道中的CD8 ⁺ T _RM细胞不是来源于循环中的T _EM细胞，而是由T _RM连续播种的。来自肺间质的细胞。此过程由CXCR6驱动，该CXCR6在T _RM细胞而非T _EM细胞上唯一表达。我们进一步证明，肺间质CD8 ⁺ T _RM细胞群体也通过稳态增殖机制独立于T _EM细胞维持。综上所述，这些数据表明，肺间质和气道中的肺记忆CD8 ⁺ T _RM细胞与T _EM细胞是部分隔开的，并阐明了其维持的机制。