(Journal Article): Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor.
 
Shin T, Kennedy G, Gorski K, Tsuchiya H, Koseki H, Azuma M, Yagita H, Chen L, Powell J, Pardoll D, Housseau F (Sidneu Kimmel Comprehensive Cancer Centre, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.)
 
IN: J Exp Med 2003; 198(1):31-38
Impact Factor(s) of J Exp Med: 14.588 (2004), 15.302 (2003), 15.34 (2001)

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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.

TYPE OF PUBLICATION: Original article

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