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Prepublished online as a Blood First Edition Paper on March 6, 2003; DOI 10.1182/blood-2002-10-3159.

Submitted November 7, 2002
Accepted February 19, 2003
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*
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA
* Corresponding author; email: klausley{at}virginia.edu.
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 LFA-1 and 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 ICAM-1 significantly inhibited adhesion of D4 cells to lung vascular endothelium and parenchyma of lung sections. However, blocking VLA-4 or 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 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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