LFA-1 is required for retention of effector CD8 T cells in mouse lungs.
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 function-associated 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.
Thatte
Jayant
J
Department of Biomedical Engineering, Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville, USA.
Dabak
Vrushali
V
Williams
Mark B
MB
Braciale
Thomas J
TJ
Ley
Klaus
K
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion; D015870:Gene Expression; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology; D039041:Integrin alpha4beta1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology; D008168:Lung / Q000166:cytology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009975:Orthomyxoviridae; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology
D006389:Hemagglutinins, Viral; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1