title: Interactions between peripheral blood CD8 T lymphocytes and intestinal epithelial cells (iEC).
abstract: 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 Vbeta 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.
authors.affiliation: Department of Molecular Immunology, Abel Salazar Institute for the Biomedical Sciences, University of Porto, Portugal.
authors.forename: F A
authors.initials: FA
authors.lastname: Arosa
authors.forename: C
authors.initials: C
authors.lastname: Irwin
authors.forename: L
authors.initials: L
authors.lastname: Mayer
authors.forename: M
authors.initials: M
authors.lastname: de Sousa
authors.forename: D N
authors.initials: DN
authors.lastname: Posnett
mesh_terms: D000328:Adult; D018106:CD28 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002448:Cell Adhesion; D002451:Cell Compartmentation; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005312:Fetal Blood; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D018106:CD28 Antigens