αEβ7 Expression on CD8+ T-Cells in COPD BAL Fluid and on TGF-β Stimulated T-Cells In Vitro

The airway inflammation in patients with COPD shows increased numbers of CD8+ T-cells. Until now few studies have shown any functional data indicating a role for these cells in the pathogenesis of COPD. This paper focuses on a subset of CD8+ T-cells present in human lung, the intra-epithelial lymphocytes expressing the integrin αEβ7, and their presence in bronchoalveolar lavage fluid from COPD patients. In this study we demonstrate that 64–89% of the CD8+ T-cells in bronchoalveolar lavage fluid from COPD patients are positive for CD103, the alpha subunit of αEβ7. We also present an in vitro system in which it is possible to differentiate peripheral T-cells into a phenotype resembling the one found in bronchoalveolar lavage fluid, i.e., CD8+ CD103+. In this in vitro system we demonstrate that, in addition to TGF-β1, cell-to-cell interaction between the T-cell and an antigen-presenting cell represented here by the monocyte, is crucial for a rapid, high and sustained expression of CD103. The signal provided by the monocytes is shown to be mediated through LFA-1 on the T-cell. Furthermore, differentiation of CD8+ T-cells by TGF-β₁ and monocytes results in down regulation of INF-γ, TNF-α and GM-CSF production. IL-8 production is, however, retained in the αEβ7 expressing cells. We see this work as an initiation on the quest for a functional characterization of one of the different types of CD8+ T cells present in COPD. In the longer perspective we hope this can lead to an increased understanding of how these cells can contribute to the disease pathology.