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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 costimulates PD1−/− CD4+ T cells. (a) Purified CD4+ T cells from wt (open bars) or PD-1 KO mice (filled bars) were stimulated with 30 ng/well of precoated anti-CD3 in the presence or absence of immobilized B7-1-Ig, B7-DC-Ig, or B7–1-Ig + B7-DC-Ig. Culture supernatants were collected at indicated times and assayed for cytokine secretion by ELISA.
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fig4: B7-DC costimulates PD1−/− CD4+ T cells. (a) Purified CD4+ T cells from wt (open bars) or PD-1 KO mice (filled bars) were stimulated with 30 ng/well of precoated anti-CD3 in the presence or absence of immobilized B7-1-Ig, B7-DC-Ig, or B7–1-Ig + B7-DC-Ig. Culture supernatants were collected at indicated times and assayed for cytokine secretion by ELISA.

Mentions: PD-1 was described as the receptor of B7-DC and B7-H1 and has been shown to negatively modulate immune responses (10, 13, 20). We therefore directly assessed the participation of PD-1 in B7-DC costimulation using CD4+ T cells from PD-1 KO mice. Fig. 4 shows that immobilized B7-DC costimulates IL-2 and IFN-γ secretion by B6 PD1−/− as well as wt B6 T cells. Moreover, the synergistic effect of B7-DC + B7–1 costimulation for cytokine production was equivalent for T cells from PD-1 KO as for wt B6 mice. This finding demonstrates that PD-1 is not necessary for the delivery of the positive costimulatory signals by B7-DC. We found that B7-DC similarly costimulates cytokine secretion by preactivated PD-1−/− CD4+ T cells similarly to wt CD4+ T cells. Finally, even in absence of PD-1 expression on preactivated T cells, the synergy between B7 and B7-DC was observed for IL-2 secretion but not for IFN-γ production as observed previously.


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 costimulates PD1−/− CD4+ T cells. (a) Purified CD4+ T cells from wt (open bars) or PD-1 KO mice (filled bars) were stimulated with 30 ng/well of precoated anti-CD3 in the presence or absence of immobilized B7-1-Ig, B7-DC-Ig, or B7–1-Ig + B7-DC-Ig. Culture supernatants were collected at indicated times and assayed for cytokine secretion by ELISA.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: B7-DC costimulates PD1−/− CD4+ T cells. (a) Purified CD4+ T cells from wt (open bars) or PD-1 KO mice (filled bars) were stimulated with 30 ng/well of precoated anti-CD3 in the presence or absence of immobilized B7-1-Ig, B7-DC-Ig, or B7–1-Ig + B7-DC-Ig. Culture supernatants were collected at indicated times and assayed for cytokine secretion by ELISA.
Mentions: PD-1 was described as the receptor of B7-DC and B7-H1 and has been shown to negatively modulate immune responses (10, 13, 20). We therefore directly assessed the participation of PD-1 in B7-DC costimulation using CD4+ T cells from PD-1 KO mice. Fig. 4 shows that immobilized B7-DC costimulates IL-2 and IFN-γ secretion by B6 PD1−/− as well as wt B6 T cells. Moreover, the synergistic effect of B7-DC + B7–1 costimulation for cytokine production was equivalent for T cells from PD-1 KO as for wt B6 mice. This finding demonstrates that PD-1 is not necessary for the delivery of the positive costimulatory signals by B7-DC. We found that B7-DC similarly costimulates cytokine secretion by preactivated PD-1−/− CD4+ T cells similarly to wt CD4+ T cells. Finally, even in absence of PD-1 expression on preactivated T cells, the synergy between B7 and B7-DC was observed for IL-2 secretion but not for IFN-γ production as observed previously.

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