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Prepublished online as a Blood First Edition Paper on June 14, 2002; DOI 10.1182/blood-2002-02-0445.

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Blood, 15 October 2002, Vol. 100, No. 8, pp. 2899-2907

IMMUNOBIOLOGY

The role of SAP in murine CD150 (SLAM)-mediated T-cell proliferation and interferon gamma  production

Duncan Howie, Susumo Okamoto, Svend Rietdijk, Kareem Clarke, Ninghai Wang, Charles Gullo, Joost P. Bruggeman, Stephen Manning, Anthony J. Coyle, Edward Greenfield, Vijay Kuchroo, and Cox Terhorst

From the Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School; Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School; Department of Neurology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; and Millennium Pharmaceuticals, Cambridge, MA.

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 TH1 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 TH1 priming, and inhibit primary TH2 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.

© 2002 by The American Society of Hematology.
 

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