The Journal of Experimental Medicine
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Published 7 July 2003. doi:10.1084/jem.20030242
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© Rockefeller University Press, 0022-1007/2003/7/31 $5.00
The Journal of Experimental Medicine, Volume 198, Number 1, 31-38

Cooperative B7-1/2 (CD80/CD86) and B7-DC Costimulation of CD4+ T Cells Independent of the PD-1 Receptor

Tahiro Shin1, Gene Kennedy1, Kevin Gorski1, Haruo Tsuchiya1, Haruhiko Koseki2,3, Miyuki Azuma4, Hideo Yagita5, Lieping Chen6, Jonathan Powell1, Drew Pardoll1 and Franck Housseau1

1 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231
2 Department of Molecular Embryology, Chiba University, Chuo-ku, Chiba 260-8670, Japan
3 RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan
4 Department of Immunology, Tokyo, Medical and Dental University, Tokyo 113-8549, Japan
5 Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8429, Japan
6 Department of Immunology, Mayo Clinic, MN 55905

Address correspondence to F. Housseau, Johns Hopkins School of Medicine, 1650 Orleans St., CRB-Rm. 440, Baltimore, MD 21231. Phone: 410-955-7866; Fax: 410-614-0549; E-mail: fhousse1{at}jhmi.edu

B7-DC is a recently discovered member of the B7 family that binds to PD-1 and is selectively expressed by dendritic cells (DCs). It has been shown to either costimulate or inhibit T cell responses. To assess the role of B7-DC in DC–T cell interactions, DCs from B7-DC knockout (KO) mice were generated and compared with DCs from wild-type (WT) and B7–1/B7–2 double KO mice. B7–1/B7–2–deficient DCs, while strongly diminished in their ability to stimulate naive CD4+ T cells, nonetheless retain partial activity. DCs from B7-DC KO mice are diminished in their ability to activate CD4+ T cells, demonstrating that DC-expressed B7-DC serves a predominantly stimulatory rather than inhibitory function in the initiation of T cell responses. B7-DC costimulates expression of CD40L with faster kinetics than B7–1 and displays potent synergy with B7–1 and B7–2 for T cell proliferation and cytokine production, indicating that these B7 family members work in concert to stimulate T cells. Finally, costimulation with B7-DC alone or in conjunction with B7–1 is PD-1 independent, indicating that B7-DC costimulates T cells via a second receptor.

Key Words: B7 • CD40L • costimulatory molecule • PD-1 • T cell activation


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