Evidence for Accessory Cell Function by Class II MHC Antigen-expressing Airway Epithelial Cells

Abstract

Expression of major histocompatibility complex (MHC) class II antigens is a requirement for accessory cell function in antigen presentation. Recent reports have demonstrated the presence of class II antigens on human bronchial epithelial cells. In the present study, immunohistochemical staining revealed HLA-DR on human airway epithelial cells obtained from two different mucosal sites (lobar bronchus and nasal turbinates). To determine whether airway epithelial cells bear functional class II molecules that allow for their cognate interaction with T lymphocytes, cells isolated from these sites were used in mixed lymphocyte cultures (MLR), as an in vitro model of accessory cell function. Freshly isolated cells (11 bronchi/3 turbinates) stimulated allogeneic T lymphocytes (stimulation index [S.I.] = 9.3 [mean]; P less than 0.001 compared to T cells alone). In order to assess the potential role of contaminating conventional accessory cells, bronchial epithelial cell isolates were first preincubated in a serum-free, growth factor-supplemented medium that functionally eliminates potential non-epithelial stimulators prior to MLR culture. Conventional accessory cell-depleted epithelial cells were still capable of stimulating allogenic T lymphocytes in 18 of 23 MLR cultures (S.I. = 5.5 [mean]; P less than 0.0005 compared to T cells alone). The addition of an anti-class II monoclonal antibody (VG2.2) at the onset of culture completely inhibited the MLR response (n = 10). No shift in the CD4+/CD8+ ratio was detected between lymphocytes harvested from airway epithelial cell MLR (1.42 +/- 1.29) and the ratio from T lymphocytes cultured alone (1.3 +/- 0.75), suggesting that both CD4+ and CD8+ T lymphocytes were proliferating in response to stimulation from alloepitopes recognized on airway epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of B7-1 and B7-2 costimulatory molecules by human gastric epithelial cells: potential role in CD4+ T cell activation during Helicobacter pylori infection.

“…Mixed epithelial cell lymphocyte culture. The allogeneic cultures were established as reported by others with some modifications (25). In brief, the gastric epithelial cells (Kato III) were irradiated with 10,000 rads to prevent their proliferation.…”

Expression of genes for B7-H3 and other T cell ligands by nasal epithelial cells during differentiation and activation

“…Whereas MHC class I is constitutively expressed by almost all cells as a part of the natural immune surveillance system, MHC class II is generally expressed on cells in association with their ability to digest foreign proteins as a part of the antigen presentation process. Class II molecules have been demonstrated on epithelial cells of the upper (17,43) and lower (17,32,34) airways. Although constitutive expression of this molecule is not consistently detectable on cells from unstimulated sources (49), reports indicate that expression of the class II molecule, human leukocyte antigen (HLA)-DR, is increased on epithelial cells in several airway inflammatory conditions, including on nasal epithelium in allergic rhinitis (33) and on bronchial epithelium in chronic bronchitis (30) and bronchial asthma (2,42).…”

Tracheal Tissue Engineering

“…Fresh tracheal allografts typically initiate a strong, acute immune rejection upon implantation [119,120,121,122]. A study by Beigel at al identified antigens within the rodent mucosa which mediate this rejection [120].…”