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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Research Article Immunology

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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RANTES/CCR5-dependent transmigration of activated effector CD8+ T cells ...
RANTES/CCR5-dependent transmigration of activated effector CD8+ T cells to alveolar interstitium. (A) Naive, early-activated, and effector CD8+ T cells were analyzed for expression of chemokine receptors. Results show the percentages (± SEM) of chemokine receptor expression for naive (white bars), early-activated (gray bars), and effector (black bars) CD8+ T cells from total expression of β-actin as a control. (B) WT recipients were injected with 1 of the following: polyclonal goat anti-RANTES Ab, polyclonal goat Ig, or PBS. After 1 hour, equal numbers of PTX-treated and nontreated effector CD8+ T cells labeled with CMTMR and CFSE were injected into recipient mice. After 4 hours, anti–CD8α-APC mAbs were injected, and 10 minutes later, lungs were harvested. Counterplots represent cells gated on CFSE+ and CMTMR+ T cells. The percentages of emigrated T cells in vascular (CFSE+/CD8-APC+, CMTMR+/CD8-APC+) and interstitial (CFSE+/CD8-APC–, CMTMR+/CD8-APC–) compartments from individual mice are shown. The percentage of emigrated interstitial labeled cells is shown in parentheses. The results are representative of 6 independent experiments. (C) Percentage of interstitial PTX-treated and control CD8+ T cells in the indicated recipients. *P < 0.05, **P < 0.001 between the percentages of interstitial nontreated T cells in nontreated mice and all other groups. (D) Effector CD8+ T cells from CCR5–/– mice and CCR5+/+ littermates were labeled with CFSE and CMTMR, respectively, mixed in ratio 1:1, and injected i.v. into recipient mice. After 7 hours, anti–CD8α-APC mAbs were injected, and 10 minutes later, lungs were harvested. Flow cytometry plots represent cells gated on CD45+ dye-labeled (CD45+/CFSE+ or CD45+/CMTMR+) cells. The percentages of lung-resident transferred CD8+ T cells in vascular (CFSE+/CD8-APC+, CMTMR+/CD8-APC+) and interstitial (CFSE+/CD8-APC–, CMTMR+/CD8-APC–) compartments are shown.