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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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Submitted February 14, 2002
Accepted June 3, 2002

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

Division of Immunology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
Inflammation Division, Millenium Pharmaceuticals Inc, Cambridge, MA, USA
Department of Adult Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
Department of Neurology, Center for Neurologic Diseases, Brigham and Womens Hospital and Harvard Medical School, Boston, MA, USA

* Corresponding author; email: dhowie{at}caregroup.harvard.edu.

CD150 (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 co-stimulation and TH1 priming we have generated a panel of rat anti-mouse CD150 monoclonal antibodies. CD150 cell-surface expression is upregulated with rapid kinetics in activated T cells and LPS/Interferon gamma activated macrophages. Anti-CD150 triggering induces strong co-stimulation 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), as anti-CD150 induces similar levels of DNA synthesis in SAP-/- T cells. Antibodies to CD150 also enhance Interferon gamma production both in wild-type and SAP-/- T cells during primary stimulation. The level of Interferon gamma production is higher in SAP-/- T cells than in wild type T cells. Anti-CD150 antibodies also synergize with IL-12 treatment in up-regulation of IL-12 receptor ß2 mRNA during TH1 priming, and inhibit primary TH2 polarization in an Interferon gamma-dependent fashion. Crosslinking 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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