Galkina Elena, Thatte Jayant, Dabak Vrushali, Williams Mark B, Ley Klaus, Braciale Thomas J
Department of Biomedical Engineering, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
J Clin Invest. 2005 Dec;115(12):3473-83. doi: 10.1172/JCI24482. Epub 2005 Nov 23.
The respiratory tract is a primary site of infection and exposure to environmental antigens and an important site of memory T cell localization. We analyzed the migration and retention of naive and activated CD8+ T cells within the noninflamed lungs and quantitated the partitioning of adoptively transferred T cells between the pulmonary vascular and interstitial compartments. Activated but not naive T cells were retained within the lungs for a prolonged period. Effector CD8+ T cells preferentially egressed from the pulmonary vascular compartment into the noninflamed pulmonary interstitium. T cell retention within the lung vasculature was leukocyte function antigen-1 dependent, while the egress of effector T cells from the vascular to the interstitium functions through a pertussis toxin-sensitive (PTX-sensitive) mechanism driven in part by constitutive CC chemokine ligand 5 expression in the lungs. These results document a novel mechanism of adhesion receptor- and pulmonary chemokine-dependent regulation of the migration of activated CD8+ T cells into an important nonlymphoid peripheral site (i.e., the normal/noninflamed lung).
呼吸道是感染和接触环境抗原的主要部位,也是记忆T细胞定位的重要部位。我们分析了未活化和活化的CD8+ T细胞在未发炎肺内的迁移和滞留情况,并对过继转移的T细胞在肺血管和间质区室之间的分配进行了定量分析。活化而非未活化的T细胞在肺内长期滞留。效应性CD8+ T细胞优先从肺血管区室进入未发炎的肺间质。T细胞在肺血管系统内的滞留依赖于白细胞功能抗原-1,而效应性T细胞从血管向间质的逸出通过一种百日咳毒素敏感(PTX敏感)机制发挥作用,该机制部分由肺中组成性CC趋化因子配体5的表达驱动。这些结果证明了一种新的机制,即粘附受体和肺趋化因子依赖的对活化CD8+ T细胞迁移至重要非淋巴外周部位(即正常/未发炎肺)的调节机制。