Locally inducible CD66a (CEACAM1) as an amplifier of the human intestinal T cell response.
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 NFkappaB 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.
Donda
A
A
Experimental Immunology, University Hospital, Basel, Switzerland.
Mori
L
L
Shamshiev
A
A
Carena
I
I
Mottet
C
C
Heim
M H
MH
Beglinger
C
C
Grunert
F
F
Rochlitz
C
C
Terracciano
L
L
Jantscheff
P
P
De Libero
G
G
D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D001692:Biological Transport; D015815:Cell Adhesion Molecules; D002460:Cell Line; D003593:Cytoplasm / Q000737:chemistry; D006031:Glycosylation; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D016328:NF-kappa B; D018808:Transcription Factor AP-1