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 c ytotoxic T cells. We asked whether the predominance of CD8(+) CD28(-) T cells in the gut may result from peripheral blood T cells preferenti ally migrating to the iIEL compartment and adhering to iEC. Compared w ith CD4 cells, adhesion of resting CD8(+) T cells to iEC cell lines wa s 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 betwe en CD8(+) CD28(+) and CD8(+) CD28(-) T cells. Thus CD8 cells may prefe rentially 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 w ith iEC cell lines and primary iEC. Induction of the CD8(+) CD28(-) ph enotype in cord blood and adult T cells was observed in co-cultures wi th iEC and also with mitogens and superantigens. In the latter case, C D28 down-modulation was seen specifically in the VP subset targeted by the superantigen, indicating that loss of CD28 expression is a direct result of T cell receptor (TCR)-mediated stimulation. The combined re sults suggest that CD8(+) CD28(-) T cells are antigen experienced T ce lls, and that they may have a survival advantage in the presence of gu t epithelial cells in vitro. This may contribute to the predominance o f CD8(+) CD28(-) T cells in the iIEL compartment.