Endothelial selectins and alpha4 integrins regulate independent pathways of T lymphocyte recruitment in the pulmonary immune response.
The cell adhesion molecules (CAMs) required for T lymphocyte recruitment during pulmonary immune responses have not been defined. Our laboratories recently reported that intratracheal (IT) challenge of sensitized mice with SRBC induced prolonged expression of vascular P-selectin, E-selectin, and VCAM-1, particularly in areas of mononuclear leukocyte infiltration. A surge in the number of circulating T lymphocytes expressing selectin ligands preceded the peak accumulation of T cells in the lung. In addition, a significant percentage of the T cells recovered from the lung expressed selectin ligands as well. The current study demonstrates that cultured T lymphoblasts use both selectin ligands and alpha4 integrins to enter the airspace and interstitium during the response to SRBC. Fluorescently labeled T lymphoblasts, derived via activation on CD3 and growth in low dose IL-2, showed inflammation-specific recruitment into lungs harvested 24 h after cell infusion. Their flux paralleled the accumulation of host lymphocytes in the lung, with both peaking 2 to 4 days after SRBC challenge. Trafficking studies conducted over a 24-h period during peak lymphocyte accumulation in the lungs revealed preferential recruitment of labeled T lymphoblasts expressing P- and E-selectin ligands. In addition, mAb blockade of the alpha4 integrins and targeted deletion of an alpha(1,3)fucosyltransferase essential for selectin ligand synthesis each reduced labeled T lymphoblast trafficking to a significant degree. Furthermore, alpha4 integrin blockade reduced the trafficking of the selectin ligand-deficient cells into the airspace, confirming that its contribution is in part independent from the vascular selectins. These findings imply that both selectin ligands and alpha4 integrins participate in T lymphoblast recruitment during the pulmonary immune response to IT SRBC.
Department of Pathology, University of Michigan Medical Center, Ann Arbor 48109, USA.
F M
FM
Wolber
J L
JL
Curtis
P
P
Mály
R J
RJ
Kelly
P
P
Smith
T A
TA
Yednock
J B
JB
Lowe
L M
LM
Stoolman
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D019040:E-Selectin / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D005260:Female; D039441:Integrin alpha4; D008168:Lung / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D015703:Antigens, CD; D019040:E-Selectin; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4