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

Abstract

CD66a is an adhesion molecule member of the carcinoembryonic antigen immunoglobulin‐like family present on the surface of epithelial cells, granulocytes 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 and IL‐15 cytokines. T cells express four different CD66a splice variants and at least two forms of the protein are glycosylated in a cell type‐specific 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 intracytoplasmic domain, which contains two immunoglobulin receptor family tyrosine‐based inhibitory motif‐like domains, as shown by stimulation of Jurkat cells transfected with different CD66a isoforms and is associated with increased induction of AP1 and NFκB transcription factors. These data indicate that CD66a amplifies T cell activation and thus could facilitate crosstalk between epithelial cells and T lymphocytes in intestinal immune response.

CEACAM1 Dynamics during Neisseria gonorrhoeae Suppression of CD4+ T Lymphocyte Activation

“…Studies performed in mice also demonstrate that CEACAM1-specific agonists inhibit Th1 and Th2 cytokine expression and immune-mediated delayed type hypersensitivity and inflammatory bowel disease in vivo (34). Although such evidence clearly indicates that CEACAM1 can inhibit T cell function, it is important to consider that certain CEACAM1-specific Abs have a costimulatory effect (35,36).…”

The Cell-Cell Adhesion Molecule Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 Inhibits IL-2 Production and Proliferation in Human T Cells by Association with Src Homology Protein-1 and Down-Regulates IL-2 Receptor

“…The binding of Neisseria to CEACAM1 on activated human T cells was shown to arrest further activation and proliferation of T cells, providing a case for inhibition (20). However, in intestinal T cells, a case has been made for both activation (21) and inhibition (22), and decidual lymphocytes that express CEACAM1 are inhibited by extravillous trophoblast cells that also express CEACAM1, perhaps leading to protection of embryonic tissue from immune attack (23). These observations, plus the unexplained role of a homophilic cell-cell adhesion in activated T cells, prompted us to further investigate the activity of CEACAM1 and its long and short cytoplasmic domain isoforms in model systems.…”

CEACAM1 : modulateur central du métabolisme, de la progression tumorale,de l’angiogenèse et de l’immunité

“…Premièrement, CEACAM1 est rapidement surexprimée à la surface des lymphocytes T après activation du complexe TCR par des cytokines telles l'IL-2 [27]. Les lymphocytes T présents dans le côlon surexpriment également CEACAM1 lors de l'inflammation de l'intestin [28]. Par ailleurs, les souris transgéniques surexprimant CEACAM1-4L spécifique-ment dans les lymphocytes T présen-tent une prolifération des lymphocytes T et une production d'IL-2 diminuées.…”