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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.

Show MeSH
BMDCs from B7-DC−/− mouse are deficient in stimulating T cells. (a) BMDCs (104/well) from wt mice (diamond), B7-DC KO mice (square), and B7–1/B7–2 double KO mouse (triangle) were cultured with CD4+ OT-II T cells (104/well) in the presence of the indicated concentrations of OVA323–339 peptide and proliferation was measured after 3 d. (b) Supernatants from these cultures with BMDCs from wt mouse (open bars), B7-DC KO mice (hatched bar), and B7–1/B7–2 double KO mice (filled bars) were collected after 2 d and IL-2 and IFN-γ were measured by ELISA.
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fig1: BMDCs from B7-DC−/− mouse are deficient in stimulating T cells. (a) BMDCs (104/well) from wt mice (diamond), B7-DC KO mice (square), and B7–1/B7–2 double KO mouse (triangle) were cultured with CD4+ OT-II T cells (104/well) in the presence of the indicated concentrations of OVA323–339 peptide and proliferation was measured after 3 d. (b) Supernatants from these cultures with BMDCs from wt mouse (open bars), B7-DC KO mice (hatched bar), and B7–1/B7–2 double KO mice (filled bars) were collected after 2 d and IL-2 and IFN-γ were measured by ELISA.

Mentions: CD4+ T cells from young OT-II transgenic mice were cocultured with DCs from either wt, B7–1/B7–2 KO, or B7-DC KO mice in the presence of varying peptide concentrations and T cell proliferation, IL-2 and IFN-γ production were measured. Fig. 1 shows that unstimulated OT-II T cells responded to OVA323–339 peptide presented by B7–1/B7–2−/− DCs although to a much lesser extent than wt DCs. These results suggested that B7–1/B7–2−/− DCs express additional molecules capable of providing costimulation to T cells. Stimulation of OT-II cells by B7-DC−/− DCs was diminished relative to wt DCs although it was greater than with B7–1/B7–2−/− DCs. In parallel with the proliferation results, IFN-γ production by OT-II cells was diminished with B7-DC−/− DCs, though not as much as with B7–1/B7–2−/− DCs. These results demonstrate that B7-DC provides a positive rather than inhibitory signal for initiating CD4+ T cell activation.


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)

BMDCs from B7-DC−/− mouse are deficient in stimulating T cells. (a) BMDCs (104/well) from wt mice (diamond), B7-DC KO mice (square), and B7–1/B7–2 double KO mouse (triangle) were cultured with CD4+ OT-II T cells (104/well) in the presence of the indicated concentrations of OVA323–339 peptide and proliferation was measured after 3 d. (b) Supernatants from these cultures with BMDCs from wt mouse (open bars), B7-DC KO mice (hatched bar), and B7–1/B7–2 double KO mice (filled bars) were collected after 2 d and IL-2 and IFN-γ were measured by ELISA.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196092&req=5

fig1: BMDCs from B7-DC−/− mouse are deficient in stimulating T cells. (a) BMDCs (104/well) from wt mice (diamond), B7-DC KO mice (square), and B7–1/B7–2 double KO mouse (triangle) were cultured with CD4+ OT-II T cells (104/well) in the presence of the indicated concentrations of OVA323–339 peptide and proliferation was measured after 3 d. (b) Supernatants from these cultures with BMDCs from wt mouse (open bars), B7-DC KO mice (hatched bar), and B7–1/B7–2 double KO mice (filled bars) were collected after 2 d and IL-2 and IFN-γ were measured by ELISA.
Mentions: CD4+ T cells from young OT-II transgenic mice were cocultured with DCs from either wt, B7–1/B7–2 KO, or B7-DC KO mice in the presence of varying peptide concentrations and T cell proliferation, IL-2 and IFN-γ production were measured. Fig. 1 shows that unstimulated OT-II T cells responded to OVA323–339 peptide presented by B7–1/B7–2−/− DCs although to a much lesser extent than wt DCs. These results suggested that B7–1/B7–2−/− DCs express additional molecules capable of providing costimulation to T cells. Stimulation of OT-II cells by B7-DC−/− DCs was diminished relative to wt DCs although it was greater than with B7–1/B7–2−/− DCs. In parallel with the proliferation results, IFN-γ production by OT-II cells was diminished with B7-DC−/− DCs, though not as much as with B7–1/B7–2−/− DCs. These results demonstrate that B7-DC provides a positive rather than inhibitory signal for initiating CD4+ T cell activation.

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