The Journal of Experimental Medicine
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Published 19 May 2003. doi:10.1084/jem.20010685
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© Rockefeller University Press, 0022-1007/2003/5/1255 $5.00
The Journal of Experimental Medicine, Volume 197, Number 10, 1255-1267

Lymphocyte Homing to Bronchus-associated Lymphoid Tissue (BALT) Is Mediated by L-selectin/PNAd, {alpha}4ß1 Integrin/VCAM-1, and LFA-1 Adhesion Pathways

Baohui Xu1,2,3, Norbert Wagner4, Linh Nguyen Pham1, Vincent Magno1, Zhongyan Shan1, Eugene C. Butcher1,2 and Sara A. Michie1,2

1 Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305
2 Pathology and Laboratory Medicine Service, Department of Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA 94304
3 Department of Environmental Medicine, Kagoshima University, Faculty of Medicine, Kagoshima 890-8520, Japan
4 Department of Pediatrics, City Hospital of Dortmund, D-44137 Dortmund, Germany

Address correspondence to Eugene C. Butcher, Dept. of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324. Phone: (650) 852-3369; Fax: (650) 858-3986; E-mail: ebutcher{at}stanford.edu

Bronchus-associated lymphoid tissue (BALT) participates in airway immune responses. However, little is known about the lymphocyte–endothelial adhesion cascades that recruit lymphocytes from blood into BALT. We show that high endothelial venules (HEVs) in BALT express substantial levels of VCAM-1, in marked contrast to HEVs in other secondary lymphoid tissues. BALT HEVs also express the L-selectin ligand PNAd. Anti–L-selectin, anti-PNAd, and anti–LFA-1 mAbs almost completely block the homing of B and T lymphocytes into BALT, whereas anti–{alpha}4 integrin and anti–VCAM-1 mAbs inhibit homing by nearly 40%. {alpha}4ß7 integrin and MAdCAM-1 are not involved. Importantly, we found that mAbs against {alpha}4 integrin and VCAM-1 significantly block the migration of total T cells (80% memory phenotype) but not naive T and B cells to BALT. These results suggest that an adhesion cascade, which includes L-selectin/PNAd, {alpha}4ß1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT. This high level of involvement of {alpha}4ß1 integrin/VCAM-1 is unique among secondary lymphoid tissues, and may help unify lymphocyte migration pathways and immune responses in BALT and other bronchopulmonary tissues.

Key Words: lung • bronchi • cell adhesion molecules • endothelium • CD106


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