Differential expression of alpha E beta 7 integrins on bronchoalveolar lavage T lymphocyte subsets: regulation by alpha 4 beta 1-integrin crosslinking and TGF-beta.

Abstract

T lymphocytes expressing the alpha E beta 7 integrin are localized and selectively retained in mucosal tissues. To investigate a potential relationship between alpha E beta 7 expression and pulmonary inflammation, the distribution of alpha E beta 7-bearing CD4+ and CD8+ T cells in peripheral blood and bronchoalveolar lavage (BAL) fluids obtained from patients with allergic asthma, sarcoidosis, hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis (IPF) was determined. In contrast to the distribution in peripheral blood, BAL fluid from these patients contained high number of cells expressing alpha E beta 7 with markedly different expression patterns on CD4 or CD8 cells as well as among the various diseases. Despite similar numbers of activated CD4 cells, alpha E beta 7+CD4+ T cells ranged from 15% in asthmatics to 70% in IPF. In contrast, even in normal individuals, 60% to 90% of BAL fluid CD8+ T cells express alpha E beta 7, suggesting differential induction mechanisms on CD4 and CD8 cells. In vitro experiments revealed that a substantial proportion of peripheral blood CD+ T cells express alpha E beta 7 after stimulation with anti-CD3 antibodies, and up to 80% positive cells were found after the addition of TGF-beta. In contrast, less than 10% of CD4 cells express this particular integrin after in vitro stimulation, and the presence of TGF-beta only increased the number to 30%. Supernatants from in vitro-activated BAL cells as well as concentrated BAL fluid from patients with high alpha E beta 7 expression had no further enhancing effect. However, crosslinking of alpha 4 beta 1-, but not beta 2-integrins, significantly increased the number of alpha E beta 7 expressing CD4+ and CD8+ T cells, even in the absence of TGF-beta. These data indicate that in addition to TGF-beta, the interaction of particular T-cell subsets with specific endothelial cell and extracellular matrix proteins may upregulate alpha E beta 7 integrin expression and thereby contribute to the selective accumulation of these cells in inflammatory lung diseases.

Phenotypic and molecular characterization of CD103+ CD4+ T cells in bronchoalveolar lavage from patients with interstitial lung diseases

“…In previous work we reported that the regulation of CD103 expression differs between CD4 ϩ and CD8 ϩ T cells. Moreover, we and others reported that the proportion of CD103 ϩ T cells in the BAL within the CD4 ϩ T-cell population increases significantly in interstitial lung diseases (8,9).…”

“…Although it is expressed on only a small proportion of blood T cells, it is induced upon activation of the T cells in the presence of transforming growth factor (TGF) ␤1 (8,18). In previous work we reported that the regulation of CD103 expression differs between CD4 ϩ and CD8 ϩ T cells.…”

“…However, in bronchoalveolar lavage fluid, the relative amount of CD103-expressing T cells is very different between CD4 ϩ and CD8 ϩ T cells. Most of the CD8 ϩ T cells express this integrin independently of the disease of the lung (8). In contrast, the proportion of CD4 ϩ T cells expressing CD103 is significantly higher in diseases associated with pulmonary fibrosis than in non-fibrotic diseases or healthy controls (8,9).…”

“…Most of the CD8 ϩ T cells express this integrin independently of the disease of the lung (8). In contrast, the proportion of CD4 ϩ T cells expressing CD103 is significantly higher in diseases associated with pulmonary fibrosis than in non-fibrotic diseases or healthy controls (8,9). However, very little is known about the phenotype of CD103 ϩ T cells and the conditions that lead to the striking accumulation of these cells in pulmonary fibrosis.…”

“…In contrast, VLA-1 and VLA-2 can be detected only several weeks after activation (10). The integrin CD103 also has been reported to be an activation marker on T cells and is expressed on the cell surface starting 2 days after in vitro activation (8). It is known that the costimulatory action of transforming growth factor (TGF) ␤1 and T-cell receptormediated signals are required for the expression of CD103.…”