Preferential migration of effector CD8+ T cells into the interstitium of the normal lung
Elena Galkina, Jayant Thatte, Vrushali Dabak, Mark B. Williams, Klaus Ley, Thomas J. Braciale
Elena Galkina, Jayant Thatte, Vrushali Dabak, Mark B. Williams, Klaus Ley, Thomas J. Braciale
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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.