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

被引：64

作者：

Howie, D

Okamoto, S

Rietdijk, S

Clarke, K

Wang, NH

Gullo, C

Bruggeman, JP

Manning, S

Coyle, AJ

Greenfield, E

Kuchroo, V

Terhorst, C

机构：

[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA

[3] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA

[4] Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA

[5] Millennium Pharmaceut, Cambridge, MA USA

来源：

BLOOD | 2002年 / 100卷 / 08期

关键词：

D O I：

10.1182/blood-2002-02-0445

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 anti-mouse CD150 monoclonal antibodies. CD150 cell surface expression is upregulated 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. 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.

引用

页码：2899 / 2907

页数：9

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