LUNG EPITHELIAL LINING FLUID T-CELL SUBSETS DEFINED BY DISTINCT PATTERNS OF BETA-7 AND BETA-1 INTEGRIN EXPRESSION

Integrins are heterodimeric cell-surface glycoproteins that mediate cell-cell and cell-matrix adhesion. We previously identified cDNA encoding a novel integrin beta subunit, beta 7, from bronchoalveolar lavage fluid (BALF) leukocytes. The beta 7 subunit protein is now known to associate with at least two integrin or subunits on lymphocytes. One beta 7 integrin, alpha 4 beta 7, mediates lymphocyte adhesion to endothelium and to fibronectin. The other known beta 7 integrin, alpha E beta 7, has recently been shown to mediate lymphocyte-epithelial cell adhesion in vitro. We used flow microfluorometry to analyze the expression of alpha 4 beta 7, and other integrins on blood T cells and epithelial lining fluid T cells obtained from five healthy adult volunteers by bronchoalveolar lavage. alpha 4 beta 7 was the predominant beta 7 integrin on blood T cells, whereas alpha E beta 7 was predominant on BALF T cells. BALF T cells could be divided into alpha E beta 7(-) and alpha E beta 7(+) subsets. Between 29 and 61% (mean 42%) of CD3(+) T cells were alpha E beta 7(+). alpha E beta 7 was more likely to be present on CD8(+) T cells (mean 69% alpha E beta 7(+)) than on CD4(+) T cells (mean 29% alpha E beta 7(+)). The alpha E beta 7(-) and alpha E beta 7(+) BALF T cell subsets were also found to differ in their expression of other integrins. Compared with alpha E beta 7(-) cells, alpha E beta 7(+) cells expressed markedly higher mean levels of the alpha 1 subunit and somewhat higher levels of the alpha 2, alpha 3, beta 1, and beta 2 subunits and the alpha 4 beta 7 complex, but lower levels of the alpha 4, alpha 5, and alpha 6 subunits. Blood T cells stimulated with phorbol ester and transforming growth factor-beta 1 in vitro developed somewhat similar patterns of alpha E beta 7 and alpha 1 expression but expressed much higher levels of alpha 4 beta 7 than did BALF T cells. These data demonstrate that subpopulations of lung epithelial lining fluid T cells express different combinations of cell adhesion receptors. These T cell subsets are likely to interact differently with other cells and with the extracellular matrix, and they may have distinct roles in the pulmonary immune response.