4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4-1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28− T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti-CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor–associated factor (TRAF)1 or TRAF2 associate with a glutathione S-transferase–4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross-linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.
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1 June 1998
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June 01 1998
CD28-independent, TRAF2-dependent Costimulation of Resting T Cells by 4-1BB Ligand
Katina Saoulli,
Katina Saoulli
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Soo Young Lee,
Soo Young Lee
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Jennifer L. Cannons,
Jennifer L. Cannons
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Wen Chen Yeh,
Wen Chen Yeh
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Angela Santana,
Angela Santana
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Marni D. Goldstein,
Marni D. Goldstein
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Naveen Bangia,
Naveen Bangia
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Mark A. DeBenedette,
Mark A. DeBenedette
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Tak W. Mak,
Tak W. Mak
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Yongwon Choi,
Yongwon Choi
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Tania H. Watts
Tania H. Watts
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
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Katina Saoulli
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Soo Young Lee
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Jennifer L. Cannons
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Wen Chen Yeh
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Angela Santana
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Marni D. Goldstein
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Naveen Bangia
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Mark A. DeBenedette
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Tak W. Mak
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Yongwon Choi
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Tania H. Watts
From the *Department of Immunology, the ‡Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the §Howard Hughes Medical Institute and ‖The Rockefeller University, New York 10021
Address correspondence to Dr. Tania H. Watts, Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada. Phone: 416-978-4551; Fax: 416-978-1938; E-mail: [email protected]
Received:
December 18 1997
Revision Received:
April 02 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 187 (11): 1849–1862.
Article history
Received:
December 18 1997
Revision Received:
April 02 1998
Citation
Katina Saoulli, Soo Young Lee, Jennifer L. Cannons, Wen Chen Yeh, Angela Santana, Marni D. Goldstein, Naveen Bangia, Mark A. DeBenedette, Tak W. Mak, Yongwon Choi, Tania H. Watts; CD28-independent, TRAF2-dependent Costimulation of Resting T Cells by 4-1BB Ligand . J Exp Med 1 June 1998; 187 (11): 1849–1862. doi: https://doi.org/10.1084/jem.187.11.1849
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