Preferential migration of effector CD8+ T cells into the interstitium of the normal lung
Elena Galkina, … , Klaus Ley, Thomas J. Braciale
Elena Galkina, … , Klaus Ley, Thomas J. Braciale
Published December 1, 2005
Citation Information: J Clin Invest. 2005;115(12):3473-3483. https://doi.org/10.1172/JCI24482.
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Preferential migration of effector CD8+ T cells into the interstitium of the normal lung

Abstract

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).

Authors

Elena Galkina, Jayant Thatte, Vrushali Dabak, Mark B. Williams, Klaus Ley, Thomas J. Braciale

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Figure 4

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Regulation of the retention time within the lungs but not transmigration...
Regulation of the retention time within the lungs but not transmigration into the interstitium by LFA-1. (A) Pretreated with anti–LFA-1 mAbs, CFSE-labeled effector CD8+ T cells were mixed with CMTMR-labeled–nontreated effector CD8+ T cells and injected into WT recipient mice. Anti–CD8α-APC mAbs were injected at 6 hours after transfer; lungs were harvested 10 minutes later. The percentages of labeled CD8+ T cells from individual mice are shown in dot plots, the percentages of interstitial cells in parentheses. Results are representative of 6 recipients from a total of 6 independent experiments. (B) CMTMR-labeled LFA-1–/– activated CD8+ T cells were mixed with equal numbers of CFSE-labeled activated (LFA-1+/+) CD8+ T cells and injected into WT recipient mice. The percentages of labeled CD8+ T cells from LFA-1–/– and LFA-1+/+ donors localized to the lungs over time are shown. CD8+ T cells were activated by plate-bound anti-CD3/CD28 Abs. Results are representative of 4 recipient mice in a total of 4 independent experiments.