The Journal of Experimental Medicine
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Published 16 May 2005. doi:10.1084/jem.20050072
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 10, 1531-1541
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ARTICLE

 In vivo costimulatory role of B7-DC in tuning T helper cell 1 and cytotoxic T lymphocyte responses

Tahiro Shin1,2, Kiyoshi Yoshimura1, Takako Shin1, Emily B. Crafton1, Haruo Tsuchiya1, Franck Housseau1, Haruhiko Koseki3, Richard D. Schulick1, Lieping Chen1,2, and Drew M. Pardoll1

1 Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231
2 Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21231
3 RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan

CORRESPONDENCE Drew M. Pardoll: dmpardol1{at}jhmi.edu

B7-DC, one of the recently described B7 family members, has the capacity to inhibit T cell responses via engagement of the immunoreceptor tyrosine-based inhibitory motif–containing inhibitory PD-1 receptor as well as enhance responses via an as yet unidentified costimulatory receptor. B7-DC is highly homologous to a coinhibitory B7 family member, B7-H1, which also binds PD-1. It is currently unclear which B7-DC function—costimulation or inhibition—predominates in vivo. To study in vivo functions of B7-DC, we evaluated immune responses in B7-DC knockout (KO) mice. Although not eliminated, interferon-{gamma} (IFN-{gamma}) production by CD4 T cells and IFN-{gamma}–dependent humoral responses were reduced in B7-DC KO mice relative to wild type mice. Antigen-specific CD8 T cell responses and cytotoxic T lymphocyte (CTL) activity were also diminished in B7-DC KO mice. Hepatic tumors grew more quickly in B7-DC KO mice, associated with a decrease in intrahepatic tumor-specific CD8 T cells. These results highlight the contrasting in vivo roles of B7-DC and B7-H1 and indicate that B7-DC functions as a tuning molecule, selectively augmenting T helper 1 and CTL responses.

Abbreviations used: BMDC, bone marrow–derived dendritic cell; CFSE, carboxyfluorescein succinimidyl; ConA, concanavalin A; HA, hemagglutinin; NOD, nonobese diabetic; PHN, peripheral hepatic nodes; PLN, peripheral lymph nodes.


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