Locally inducible CD66a (CEACAM1) as an amplifier of the human intestinal T cell response

CD66a is an adhesion molecule member of the carcinoembryonic antigen immuno globulinlike family present on the surface of epithelial cells, granulocyte s and IL-2 activated T cells. We studied whether CD66a is expressed in vivo by T lymphocytes and whether it affects TCR-mediated activation. CD66a was detected by histochemistry, flow cytometry analysis, reverse transcription PCR and Western blot on fresh colon biopsies and T cell clones. A fraction of T cells in the lamina propria express CD66a, which is induced by IL-7 a nd IL-15 cytokines. T cells express four different CD66a splice variants an d at least two forms of the protein are glycosylated in a cell type-specifi c manner. Triggering of CD66a on T cells with physiological ligands or with specific mAb increases TCR-mediated lymphokine release, in an antigen dose -independent manner. This effect requires the presence of the CD66a intracy toplasmic domain, which contains two immunoglobulin receptor family tyrosin e-based inhibitory motif-like domains, as shown by stimulation of Jurkat ce lls transfected with different CD66a isoforms and is associated with increa sed induction of AP1 and NF kappa B transcription factors. These data indic ate that CD66a amplifies T cell activation and thus could facilitate crosst alk between epithelial cells and T lymphocytes in intestinal immune respons e.