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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 - J. Exp. Med. (2003)

Bottom Line: B7-1/B7-2-deficient DCs, while strongly diminished in their ability to stimulate naive CD4+ T cells, nonetheless retain partial activity.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.

View Article: PubMed Central - PubMed

Affiliation: Sidneu Kimmel Comprehensive Cancer Centre, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.

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.

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Related in: MedlinePlus

B7-DC and anti-CD28 mAb synergize for costimulation of IL-2 production even in the presence of high levels of PD-1. (a) AE-7 cells, which express high level of PD-1 were cultured in presence of limiting amounts of immobilized anti-CD3 with either B7-DC-Ig, B7–1-Ig, anti-CD28 (at limiting concentration), or indicated combinations. (b) Culture supernatants were collected at 24 h and assayed for IL-2 by ELISA.
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fig5: B7-DC and anti-CD28 mAb synergize for costimulation of IL-2 production even in the presence of high levels of PD-1. (a) AE-7 cells, which express high level of PD-1 were cultured in presence of limiting amounts of immobilized anti-CD3 with either B7-DC-Ig, B7–1-Ig, anti-CD28 (at limiting concentration), or indicated combinations. (b) Culture supernatants were collected at 24 h and assayed for IL-2 by ELISA.

Mentions: Synergistic effects between B7–1 and B7-DC on activation of the T cell clone AE-7, which expresses constitutively high level of PD-1, were assessed using plate bound anti-CD3 in presence of anti-CD28 or B7–1 and/or B7-DC. Fig. 5 demonstrates that, even in the presence of much higher levels of PD-1 than typically observed on activated splenic or LN T cells directly out of the mouse, B7-DC synergizes very efficiently for costimulation of IL-2 production. These results suggest that interaction of B7-DC with the alternate receptor may override PD-1 mediated effects.


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 - J. Exp. Med. (2003)

B7-DC and anti-CD28 mAb synergize for costimulation of IL-2 production even in the presence of high levels of PD-1. (a) AE-7 cells, which express high level of PD-1 were cultured in presence of limiting amounts of immobilized anti-CD3 with either B7-DC-Ig, B7–1-Ig, anti-CD28 (at limiting concentration), or indicated combinations. (b) Culture supernatants were collected at 24 h and assayed for IL-2 by ELISA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196092&req=5

fig5: B7-DC and anti-CD28 mAb synergize for costimulation of IL-2 production even in the presence of high levels of PD-1. (a) AE-7 cells, which express high level of PD-1 were cultured in presence of limiting amounts of immobilized anti-CD3 with either B7-DC-Ig, B7–1-Ig, anti-CD28 (at limiting concentration), or indicated combinations. (b) Culture supernatants were collected at 24 h and assayed for IL-2 by ELISA.
Mentions: Synergistic effects between B7–1 and B7-DC on activation of the T cell clone AE-7, which expresses constitutively high level of PD-1, were assessed using plate bound anti-CD3 in presence of anti-CD28 or B7–1 and/or B7-DC. Fig. 5 demonstrates that, even in the presence of much higher levels of PD-1 than typically observed on activated splenic or LN T cells directly out of the mouse, B7-DC synergizes very efficiently for costimulation of IL-2 production. These results suggest that interaction of B7-DC with the alternate receptor may override PD-1 mediated effects.

Bottom Line: B7-1/B7-2-deficient DCs, while strongly diminished in their ability to stimulate naive CD4+ T cells, nonetheless retain partial activity.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.

View Article: PubMed Central - PubMed

Affiliation: Sidneu Kimmel Comprehensive Cancer Centre, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.

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.

Show MeSH
Related in: MedlinePlus