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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Migration of effector CD8+ T cells into the lung interstitium is PTX-sen...
Migration of effector CD8+ T cells into the lung interstitium is PTX-sensitive. PTX-pretreated effector CD8+ T cells or nontreated effector CD8+ T cells were labeled with CFSE and CMTMR, mixed equally, and injected into WT recipient mice. Anti–CD8α-APC mAbs were injected at indicated time points after transfer, and lungs were harvested 10 minutes later. The percentages of total labeled, PTX-treated or control T cells retained in the lungs over time from individual recipient are indicated. The percentages of cells localized to the interstitium (CFSE+/CD8α-APC–, CMTMR+/CD8α-APC–) are shown in parentheses. Results represent the mean ± SEM from 3 to 9 recipient mice for each time point. In control experiments, cells were treated with mutant PTX (PT9K 129G, provided by E. Hewlett, University of Virginia, Charlottesville, Virginia, USA).