Interactions between peripheral blood CD8 T lymphocytes and intestinal epithelial cells (iEC)
Intestinal intraepithelial lymphocytes (iIEL) are primarily CD8 cells and most of them have a CD28− phenotype, the phenotype of effector cytotoxic T cells. We asked whether the predominance of CD8+ CD28− T cells in the gut may result from peripheral blood T cells preferentially migrating to the iIEL compartment and adhering to iEC. Compared with CD4 cells, adhesion of resting CD8+ T cells to iEC cell lines was significantly higher. Adhesion could be blocked with a MoAb to gp180, a molecule expressed on iEC which is known to interact with CD8/lck. No significant difference in the level of adhesion was observed between CD8+ CD28+ and CD8+ CD28− T cells. Thus CD8 cells may preferentially migrate to the iIEL compartment, but loss of CD28 expression could occur in situ after migration. Consistent with this hypothesis, the CD8+ CD28− cells became enriched after co‐culturing T cells with iEC cell lines and primary iEC. Induction of the CD8+ CD28− phenotype in cord blood and adult T cells was observed in co‐cultures with iEC and also with mitogens and superantigens. In the latter case, CD28 down‐modulation was seen specifically in the Vβ subset targeted by the superantigen, indicating that loss of CD28 expression is a direct result of T cell receptor (TCR)‐mediated stimulation. The combined results suggest that CD8+ CD28− T cells are antigen experienced T cells, and that they may have a survival advantage in the presence of gut epithelial cells in vitro. This may contribute to the predominance of CD8+ CD28− T cells in the iIEL compartment.