Activation-induced expression of carcinoembryonic antigen-cell adhesion molecule 1 regulates mouse T lymphocyte function.

Abstract

Carcinoembryonic Ag cell adhesion molecule 1 (CEACAM1) consists of highly related homologs in humans and rodents that are characterized by significant alternate splicing generating isoforms capable of negative intracellular signaling by virtue of two immunoreceptor tyrosine-based inhibition motifs in its cytoplasmic (cyt) tail. Although human T cells have been recently observed to express CEACAM1, the expression and function of CEACAM1 in mouse T cells have not been defined. Although resting mouse spleen T cells exhibited no evidence of CEACAM1 on the cell surface, CEACAM1 was rapidly up-regulated on CD4+ and CD8+ T cells after activation with either Con A or anti-CD3 without a requirement for either de novo transcription or translation due to the fact that CEACAM1 was present intracellularly before activation. Using a GST-CEACAM1-cytoplasmic tail fusion protein, it was shown that the cytoplasmic tail of CEACAM1 bound the src homology domain-containing phosphatase 1 and adaptor protein 1 complex in its phosphorylated and nonphosphorylated states, respectively. CEACAM1 ligation with an anti-CEACAM1 mAb resulted in inhibition of an allogeneic MLR and anti-CD3 plus anti-CD28 Ab-induced proliferation of spleen T cells in vitro and inhibition of a delayed-type hypersensitivity response to oxazolone in vivo. Inhibition of the delayed-type hypersensitivity response required that the anti-CEACAM1-specific mAb be present at the time of T cell sensitization. These studies support a role for CEACAM1 as a novel class of immunoreceptor tyrosine-based inhibition motif-bearing regulatory molecules on T cells that are active during early phases of the immune response in mice.

• Authors: Atsushi Nakajima, Hideki Iijima, Markus F Neurath, Takashi Nagaishi, Edward E S Nieuwenhuis, Raktima Raychowdhury, Jonathan Glickman, Dianna M Blau, Sara Russell, Kathryn V Holmes, Richard S Blumberg
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 168 Issue 3 Pg. 1028-35 (Feb 01 2002) ISSN: 0022-1767 [Print] United States
• PMID: 11801635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adaptor Proteins, Vesicular Transport
• Antibodies, Monoclonal
• Antigens, CD
• Antigens, Differentiation
• CD66 antigens
• Carcinoembryonic Antigen
• Carrier Proteins
• Ceacam1 protein, mouse
• Cell Adhesion Molecules
• Intracellular Signaling Peptides and Proteins
• Ligands
• Membrane Proteins
• Protein Phosphatase 1
• PTPN11 protein, human
• PTPN6 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 11
• Protein Tyrosine Phosphatase, Non-Receptor Type 6
• Protein Tyrosine Phosphatases
• Ptpn11 protein, mouse
• Ptpn6 protein, mouse
• SH2 Domain-Containing Protein Tyrosine Phosphatases

Topics

• Adaptor Proteins, Vesicular Transport
• Animals
• Antibodies, Monoclonal (administration & dosage)
• Antigens, CD (biosynthesis, immunology, metabolism, physiology)
• Antigens, Differentiation (biosynthesis, immunology, metabolism, physiology)
• Carcinoembryonic Antigen (biosynthesis, immunology, metabolism, physiology)
• Carrier Proteins (metabolism)
• Cell Adhesion Molecules (biosynthesis, immunology, metabolism, physiology)
• Cell Membrane (immunology, metabolism)
• Cells, Cultured
• Injections, Intraperitoneal
• Interphase (immunology)
• Intracellular Signaling Peptides and Proteins
• Ligands
• Lymphocyte Activation
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Protein Phosphatase 1
• Protein Tyrosine Phosphatase, Non-Receptor Type 11
• Protein Tyrosine Phosphatase, Non-Receptor Type 6
• Protein Tyrosine Phosphatases (metabolism)
• SH2 Domain-Containing Protein Tyrosine Phosphatases
• T-Lymphocytes (cytology, immunology, metabolism)
• Time Factors
• src Homology Domains (immunology)