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Prepublished online as a Blood First Edition Paper on March 6, 2003; DOI 10.1182/blood-2002-10-3159.
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Blood, 15 June 2003, Vol. 101, No. 12, pp. 4916-4922
IMMUNOBIOLOGY
LFA-1 is required for retention of effector CD8 T cells in mouse lungs
Jayant Thatte,
Vrushali Dabak,
Mark B. Williams,
Thomas J. Braciale, and
Klaus Ley
From the Department of Biomedical Engineering, Beirne B. Carter Center for Immunology Research, the Department of Radiology, and the Cardiovascular Research Center, University of Virginia Health Sciences Center, Charlottesville, VA.
The adhesion molecules involved in the migration and retention of activated effector CD8 T cells in the lung microcirculation and their recruitment into lung tissue are largely unknown. Here, we have analyzed the role of lymphocyte functionassociated antigen-1 (LFA-1) and very late antigen-4 (VLA-4) on adhesion of influenza hemagglutinin (HA)specific CD8 T-cell clone D4 under shear conditions in an in vitro binding assay and in an in vivo homing assay to the lungs of naive or transgenic Balb/c mice expressing HA (HA-Tg) by a lung-specific promoter. Blocking LFA-1 or intercellular adhesion molecule 1 (ICAM-1) significantly inhibited adhesion of D4 cells to lung vascular endothelium and parenchyma of lung sections. However, blocking VLA-4 or vascular cell adhesion molecule 1 (VCAM-1) had no effect on cell adhesion. Blocking LFA-1 in vivo significantly delayed lethal injury following adoptive transfer of D4 cells into HA-Tg mice as assessed by weight loss and histology. Residence time of adoptively transferred Indium 111 (111In)labeled D4 cells in lungs of normal and HA-Tg mice as analyzed by dual modality imaging revealed a significantly shorter transit time of 4 hours for the D4 cells upon in vivo blockade of LFA-1. These results demonstrate a crucial role for LFA-1 in retention of activated CD8 T cells in normal mouse lungs and in the progression of lethal injury in HA-Tg mice.

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