Abstract
BackgroundBronchus-associated lymphoid tissue (BALT) is the secondary lymphoid tissue in bronchial mucosa and is involved in the development of bronchopulmonary immune responses. Although migration of lymphocytes from blood vessels into secondary lymphoid tissues is critical for the development of appropriate adaptive immunity, the endothelia and lymphocyte adhesion molecules that recruit specific subsets of lymphocytes into human BALT are not known. The aim of this study was to determine which adhesion molecules are expressed on lymphocytes and high endothelial venules (HEVs) in human BALT.MethodsWe immunostained frozen sections of BALT from lobectomy specimens from 17 patients with lung carcinoma with a panel of monoclonal antibodies to endothelia and lymphocyte adhesion molecules.ResultsSections of BALT showed B cell follicles surrounded by T cells. Most BALT CD4+ T cells had a CD45RO+ memory phenotype. Almost all BALT B cells expressed α4 integrin and L-selectin. In contrast, 43% of BALT T cells expressed α4 integrin and 20% of BALT T cells expressed L-selectin. Almost all BALT lymphocytes expressed LFA-1. HEVs, which support the migration of lymphocytes from the bloodstream into secondary lymphoid tissues, were prominent in BALT. All HEVs expressed peripheral node addressin, most HEVs expressed vascular cell adhesion molecule-1, and no HEVs expressed mucosal addressin cell adhesion molecule-1.ConclusionHuman BALT expresses endothelia and lymphocyte adhesion molecules that may be important in recruiting naive and memory/effector lymphocytes to BALT during protective and pathologic bronchopulmonary immune responses.
Highlights
Bronchus-associated lymphoid tissue (BALT) is the secondary lymphoid tissue in bronchial mucosa and is involved in the development of bronchopulmonary immune responses
Most BALT CD4+ T cells had a memory phenotype. These results suggest that human BALT expresses endothelia and lymphocyte adhesion molecules that may be important in recruiting naive and memory/effector lymphocytes to BALT, where they may be involved in the initiation of bronchopulmonary immune responses to inhaled antigens and pathogens
We examined BALT T cells and B cells for the expression of L-selectin, which binds to peripheral node addressin (PNAd); α4 integrin, which is a subunit of α4β1 integrin and α4β7 integrin; and LFA-1, which binds to ICAM-1 and ICAM-2 [1]
Summary
Bronchus-associated lymphoid tissue (BALT) is the secondary lymphoid tissue in bronchial mucosa and is involved in the development of bronchopulmonary immune responses. Migration of lymphocytes from blood vessels into secondary lymphoid tissues is critical for the development of appropriate adaptive immunity, the endothelia and lymphocyte adhesion molecules that recruit specific subsets of lymphocytes into human BALT are not known. In the initiation stage of an adaptive immune response, naive T cells migrate through blood vessel high endothelia venules (HEVs) into secondary lymphoid tissues, where they are stimulated by antigen-bearing dendritic cells. This leads to the generation of antigen-specific effector and memory T cells and B cells, which are released from the secondary lymphoid tissue into the bloodstream. The presence and frequency of BALT in normal lungs of healthy adult humans is controversial [5,14,15,16,17,18,19,20]
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