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More MS news articles for March 2004

NTB-A, a new activating receptor in T cells that regulates autoimmune disease

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14988414&dopt=Abstract

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http://www.jbc.org/cgi/reprint/M312313200v1.pdf

J Biol Chem. 2004 Feb 26
Valdez PA, Wang H, Seshasayee D, Van Lookeren Campagne M, Gurney A, Lee WP, Grewal IS.
Immunology, Genetech, South San Francisco, CA 94080.

The CD28 co-stimulatory pathway is well established for T cell activation; however, results from CD28 -/- mice suggest the existence of additional co-stimulatory pathways.

Here we report the further characterization of a new member of the CD2 superfamily, NTB-A, important in T cell co-stimulation.

NTB-A is expressed on T cells and its expression is upregulated on activated cells.

Triggering of NTB-A with monoclonal antibodies in the absence of CD28 signals leads to T cell proliferation and IFN-g secretion but not IL-4.

Crosslinking of NTB-A also induces phosphorylation of NTB-A and the association of SAP, the protein absent in X-linked lymphoproliferative disease.

T helper cells differentiated by crosslinking NTB-A and CD3 developed predominately into Th1 cells, not Th2 cells.

In vivo blocking of NTB-A interactions with its ligands by using soluble NTB-A-Fc fusion protein inhibits B cell isotype switching to IgG2a and IgG3, commonly induced by Th1-type cytokines.

Importantly, treatment of mice with NTB-A-Fc delays the onset of antigen-induced experimental allergic encephalomyelitis (EAE) in MBP-TCR transgenic mice, suggesting a role in T cell mediated autoimmune disease.

Regulation of IFN-g secretion, and not IL-4 in vitro, as well as inhibition Th1 cell induced isotype switching and attenuation of EAE, indicates that NTB-A is important for Th1 responses.

The observation that crosslinking of NTB-A induces T cell activation, expansion and Th1-type cytokine production suggests NTB-A is a novel co-stimulatory receptor.

The identification of NTB-A as a regulator of T cell response paves the way to provide novel therapeutic approaches for modulation of the immune response.