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The role of SAP in murine CD150 (SLAM)-mediated T-cell proliferation and interferon gamma production.
Howie, Duncan; Okamoto, Susumo; Rietdijk, Svend; Clarke, Kareem; Wang, Ninghai; Gullo, Charles; Bruggeman, Joost P; Manning, Stephen; Coyle, Anthony J; Greenfield, Edward; Kuchroo, Vijay; Terhorst, Cox.
Afiliación
  • Howie D; Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Cambridge, MA 02215, USA. dhowie@caregroup.harvard.edu
Blood ; 100(8): 2899-907, 2002 Oct 15.
Article en En | MEDLINE | ID: mdl-12351401
CD150 (signaling lymphocyte activation molecule [SLAM]) is a self-ligand cell surface glycoprotein expressed on T cells, B cells, macrophages, and dendritic cells. To further explore the role of CD150 signaling in costimulation and T(H)1 priming we have generated a panel of rat antimouse CD150 monoclonal antibodies. CD150 cell surface expression is up-regulated with rapid kinetics in activated T cells and lipopolysaccharide/interferon gamma (IFN-gamma)-activated macrophages. Anti-CD150 triggering induces strong costimulation of T cells triggered through CD3. DNA synthesis of murine T cells induced by anti-CD150 is not dependent on SLAM-associated protein (SAP, SH2D1A), because anti-CD150 induces similar levels of DNA synthesis in SAP(-/-) T cells. Antibodies to CD150 also enhance IFN-gamma production both in wild-type and SAP(-/-) T cells during primary stimulation. The level of IFN-gamma production is higher in SAP(-/-) T cells than in wild-type T cells. Anti-CD150 antibodies also synergize with interleukin 12 (IL-12) treatment in up-regulation of IL-12 receptor beta(2) mRNA during T(H)1 priming, and inhibit primary T(H)2 polarization in an IFN-gamma-dependent fashion. Cross-linking CD150 on CD4 T cells induces rapid serine phosphorylation of Akt/PKB. We speculate that this is an important pathway contributing to CD150-mediated T-cell proliferation.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulinas / Glicoproteínas / Activación de Linfocitos / Linfocitos T / Proteínas Portadoras / Interferón gamma / Péptidos y Proteínas de Señalización Intracelular Límite: Animals Idioma: En Revista: Blood Año: 2002 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulinas / Glicoproteínas / Activación de Linfocitos / Linfocitos T / Proteínas Portadoras / Interferón gamma / Péptidos y Proteínas de Señalización Intracelular Límite: Animals Idioma: En Revista: Blood Año: 2002 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos