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Molecular and Functional Characterization of Mouse Signaling Lymphocytic Activation Molecule (SLAM): Differential Expression and Responsiveness in Th1 and Th2 Cells

Antonio G. Castro, Thomas M. Hauser, Benjamin G. Cocks, John Abrams, Sandra Zurawski, Tatyana Churakova, Francesca Zonin, Douglas Robinson, Stuart G. Tangye, Gregorio Aversa, Kim E. Nichols, Jan E. de Vries, Lewis L. Lanier and Anne O’Garra
J Immunol December 1, 1999, 163 (11) 5860-5870;
Antonio G. Castro
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Thomas M. Hauser
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Benjamin G. Cocks
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John Abrams
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Sandra Zurawski
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Tatyana Churakova
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Francesca Zonin
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Douglas Robinson
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Stuart G. Tangye
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Gregorio Aversa
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Kim E. Nichols
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Jan E. de Vries
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Lewis L. Lanier
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Anne O’Garra
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Abstract

Optimal T cell activation and expansion require engagement of the TCR plus costimulatory signals delivered through accessory molecules. SLAM (signaling lymphocytic activation molecule), a 70-kDa costimulatory molecule belonging to the Ig superfamily, was defined as a human cell surface molecule that mediated CD28-independent proliferation of human T cells and IFN-γ production by human Th1 and Th2 clones. In this study, we describe the cloning of mouse SLAM and the production of mAb against it which reveal its expression on primary mouse T and B cells. Mouse SLAM is expressed on highly polarized Th1 and Th2 populations, and is maintained on Th1, but not on Th2 clones. Anti-mouse SLAM mAb augmented IFN-γ production by Th1 cells and Th1 clones stimulated through the TCR, but did not induce IFN-γ production by Th2 cells, nor their production of IL-4 or their proliferation. Mouse SLAM is a 75-kDa glycoprotein that upon tyrosine phosphorylation associates with the src homology 2-domain-containing protein tyrosine phosphatase SHP-2, but not SHP-1. Mouse SLAM also associates with the recently described human SLAM-associated protein. These studies may provide new insights into the regulation of Th1 responses.

  • Received June 22, 1999.
  • Accepted September 15, 1999.
  • Copyright © 1999 by The American Association of Immunologists
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The Journal of Immunology: 163 (11)
The Journal of Immunology
Vol. 163, Issue 11
1 Dec 1999
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Molecular and Functional Characterization of Mouse Signaling Lymphocytic Activation Molecule (SLAM): Differential Expression and Responsiveness in Th1 and Th2 Cells
Antonio G. Castro, Thomas M. Hauser, Benjamin G. Cocks, John Abrams, Sandra Zurawski, Tatyana Churakova, Francesca Zonin, Douglas Robinson, Stuart G. Tangye, Gregorio Aversa, Kim E. Nichols, Jan E. de Vries, Lewis L. Lanier, Anne O’Garra
The Journal of Immunology December 1, 1999, 163 (11) 5860-5870;

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Molecular and Functional Characterization of Mouse Signaling Lymphocytic Activation Molecule (SLAM): Differential Expression and Responsiveness in Th1 and Th2 Cells
Antonio G. Castro, Thomas M. Hauser, Benjamin G. Cocks, John Abrams, Sandra Zurawski, Tatyana Churakova, Francesca Zonin, Douglas Robinson, Stuart G. Tangye, Gregorio Aversa, Kim E. Nichols, Jan E. de Vries, Lewis L. Lanier, Anne O’Garra
The Journal of Immunology December 1, 1999, 163 (11) 5860-5870;
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