4.8 Article

Preferential migration of effector CD8+ T cells into the interstitium of the normal lung

Journal

JOURNAL OF CLINICAL INVESTIGATION
Volume 115, Issue 12, Pages 3473-3483

Publisher

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI24482

Keywords

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Funding

  1. NHLBI NIH HHS [HL-71875, R01 HL033391, HL-54136, HL-33391, R01 HL071875] Funding Source: Medline
  2. NIAID NIH HHS [R01 AI015608, T32 AI007496, R37 AI015608, AI-15608, R01 AI037293] Funding Source: Medline

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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 C]138 T cells into an important nonlymphoid peripheral site (i.e., the normal/noninflamed lung).

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