Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor

Tahiro Shin, Gene Kennedy, Kevin Gorski, Haruo Tsuchiya, Haruhiko Koseki, Miyuki Azuma, Hideo Yagita, Lieping Chen, Jonathan Powell, Drew Pardoll, Franck Housseau

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)31-38
Number of pages8
JournalJournal of Experimental Medicine
Volume198
Issue number1
DOIs
StatePublished - Jul 7 2003

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Keywords

  • B7
  • CD40L
  • Costimulatory molecule
  • PD-1
  • T cell activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Shin, T., Kennedy, G., Gorski, K., Tsuchiya, H., Koseki, H., Azuma, M., Yagita, H., Chen, L., Powell, J., Pardoll, D., & Housseau, F. (2003). Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor. Journal of Experimental Medicine, 198(1), 31-38. https://doi.org/10.1084/jem.20030242