Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin/PNAd, alpha4beta1 integrin/VCAM-1, and LFA-1 adhesion pathways.
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-alpha4 integrin and anti-VCAM-1 mAbs inhibit homing by nearly 40%. alpha4beta7 integrin and MAdCAM-1 are not involved. Importantly, we found that mAbs against alpha4 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, alpha4beta1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT. This high level of involvement of alpha4beta1 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.
Xu
Baohui
B
Dept. of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA. ebutcher@stanford.edu
Wagner
Norbert
N
Pham
Linh Nguyen
LN
Magno
Vincent
V
Shan
Zhongyan
Z
Butcher
Eugene C
EC
Michie
Sara A
SA
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D001980:Bronchi / Q000276:immunology*; D002465:Cell Movement; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1 / Q000502:physiology*; D016023:Integrins / Q000502:physiology; D019041:L-Selectin / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology*; D008221:Lymphoid Tissue / Q000276:immunology*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D051381:Rats; D017207:Rats, Sprague-Dawley; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
D000954:Antigens, Surface; D039041:Integrin alpha4beta1; D016023:Integrins; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7; D019041:L-Selectin