Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1

Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a cell surface molecule that has been proposed to negatively regulate T cell function. We have shown that CEACAM1 is associated with specific regulation of T helper cell (Th)1 pathways, T-bet-mediated Th1 cytokine signaling,...

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Bibliographic Details
Published in:The Journal of experimental medicine 2004-02, Vol.199 (4), p.471-482
Main Authors: Iijima, Hideki, Neurath, Markus F, Nagaishi, Takashi, Glickman, Jonathan N, Nieuwenhuis, Edward E, Nakajima, Atsushi, Chen, Daohong, Fuss, Ivan J, Utku, Nalan, Lewicki, Daniel N, Becker, Christoph, Gallagher, Thomas M, Holmes, Kathryn V, Blumberg, Richard S
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Carcinoembryonic Antigen - immunology
Colitis - chemically induced
Colitis - immunology
Colitis - pathology
Disease Models, Animal
Female
Immunoglobulin Fc Fragments - immunology
Inflammation - immunology
Inflammation - pathology
Interferon-gamma - deficiency
Interferon-gamma - genetics
Interleukin-1 - deficiency
Interleukin-1 - genetics
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Murine hepatitis virus
Oxazolone
Recombinant Fusion Proteins - immunology
T-Lymphocytes, Helper-Inducer - immunology
Th1 Cells - immunology
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Summary:Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a cell surface molecule that has been proposed to negatively regulate T cell function. We have shown that CEACAM1 is associated with specific regulation of T helper cell (Th)1 pathways, T-bet-mediated Th1 cytokine signaling, and Th1-mediated immunopathology in vivo. Mice treated with anti-mouse CEACAM1-specific monoclonal antibody (mAb) CC1 during the effector phase exhibited a reduced severity of trinitrobenzene sulfonic acid colitis in association with decreased interferon (IFN)-gamma production. Although oxazolone colitis has been reported as Th2 mediated, mice treated with the CC1 mAb or a CEACAM1-Fc chimeric protein exhibited a reduced severity of colitis in association with a significant reduction of IFN-gamma and T-bet activation, whereas signal transducer and activator of antigen 4 activation was unaffected. Both interleukin-4 and IFN-gamma gene-deficient mice exhibited less severe colitis induction by oxazolone. Direct ligation of T cells in vitro with the murine hepatitis virus spike protein, a natural ligand for the N-domain of CEACAM1, inhibited the differentiation of naive cells into Th1 but not Th2 cells and activation of Th1 but not Th2 cytokine production. These results indicate that CEACAM1 isoforms are a novel class of activation-induced cell surface molecules on T cells that function in the specific regulation of Th1-mediated inflammation such as that associated with inflammatory bowel disease.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20030437