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A potential new pathway for PD-L1 costimulation of the CD8-T cell response to Listeria monocytogenes infection.

Xu D, Fu HH, Obar JJ, Park JJ, Tamada K, Yagita H, Lefran├žois L - PLoS ONE (2013)

Bottom Line: However, PD-L1 can also act as a positive costimulator, but the relevant counterreceptor is not known.Simultaneous CD4-T cell depletion and anti-PD-L1 blockade revealed that PD-L1 provided costimulation even in the absence of CD4-T cells.Most importantly, specific blockade of PD-L1 binding to CD80 or to PD-1 did not recapitulate PDL-1 blockade.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, United States of America.

ABSTRACT
Programmed death ligand-1 (PD-L1) is an important negative regulator of T cell immune responses via interactions with PD-1 and CD80. However, PD-L1 can also act as a positive costimulator, but the relevant counterreceptor is not known. We analyzed the role of PD-L1 in CD8-T cell responses to infection with Listeria monocytogenes (LM) or vesicular stomatitis virus (VSV). PD-L1 blockade impaired antigen-specific CD8 effector T cell expansion in response to LM, but not to VSV infection, particularly limiting short-lived effector cell differentiation. Simultaneous CD4-T cell depletion and anti-PD-L1 blockade revealed that PD-L1 provided costimulation even in the absence of CD4-T cells. Most importantly, specific blockade of PD-L1 binding to CD80 or to PD-1 did not recapitulate PDL-1 blockade. The results suggested that PD-L1 plays an important costimulatory role for antigen-specific CD8 T cells during LM infection perhaps through a distinct receptor or interaction epitope.

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Related in: MedlinePlus

PD-L1 augments Ag-specific CD8 T cell proliferation.A, and B, Brdu incorporation of OVA tetramer+CD8+ T cells. Mice were administered BrdU 16 hrs before sacrificing on day 5 after i.v. LM infection with or without PD-L1 blockade. C. Annexin V staining of tetramer+ cells. Data were analyzed by Student's t test, (**p<0.01). Data are representative of three independent experiments with five mice per group.
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pone-0056539-g006: PD-L1 augments Ag-specific CD8 T cell proliferation.A, and B, Brdu incorporation of OVA tetramer+CD8+ T cells. Mice were administered BrdU 16 hrs before sacrificing on day 5 after i.v. LM infection with or without PD-L1 blockade. C. Annexin V staining of tetramer+ cells. Data were analyzed by Student's t test, (**p<0.01). Data are representative of three independent experiments with five mice per group.

Mentions: To further understand the mechanism of PD-L1 costimulation we examined early proliferation of antigen-specific CD8 T cells. To this end, we administered BrdU to infected mice 16hrs before sacrifice with or without PD-L1 blockade. Incorporation of BrdU into CD8 T cells was analyzed on day 5 post-infection(Fig. 6A,B). While most tetramer+ cells from the control mice incorporated BrdU, fewer cells incorporated BrdU after PD-L1 blockade (Fig. 6A). Furthermore, in those Ova/Kb-specific CD8 T cells that did incorporate BrdU during PD-L1 blockade the level of incorporation was reduced (Fig. 6B). Using annexin V staining, no difference in apoptosis was observed between the groups (Fig. 6C). Thus, PD-L1 costimulation operated via enhancement of proliferative pathways.


A potential new pathway for PD-L1 costimulation of the CD8-T cell response to Listeria monocytogenes infection.

Xu D, Fu HH, Obar JJ, Park JJ, Tamada K, Yagita H, Lefran├žois L - PLoS ONE (2013)

PD-L1 augments Ag-specific CD8 T cell proliferation.A, and B, Brdu incorporation of OVA tetramer+CD8+ T cells. Mice were administered BrdU 16 hrs before sacrificing on day 5 after i.v. LM infection with or without PD-L1 blockade. C. Annexin V staining of tetramer+ cells. Data were analyzed by Student's t test, (**p<0.01). Data are representative of three independent experiments with five mice per group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569435&req=5

pone-0056539-g006: PD-L1 augments Ag-specific CD8 T cell proliferation.A, and B, Brdu incorporation of OVA tetramer+CD8+ T cells. Mice were administered BrdU 16 hrs before sacrificing on day 5 after i.v. LM infection with or without PD-L1 blockade. C. Annexin V staining of tetramer+ cells. Data were analyzed by Student's t test, (**p<0.01). Data are representative of three independent experiments with five mice per group.
Mentions: To further understand the mechanism of PD-L1 costimulation we examined early proliferation of antigen-specific CD8 T cells. To this end, we administered BrdU to infected mice 16hrs before sacrifice with or without PD-L1 blockade. Incorporation of BrdU into CD8 T cells was analyzed on day 5 post-infection(Fig. 6A,B). While most tetramer+ cells from the control mice incorporated BrdU, fewer cells incorporated BrdU after PD-L1 blockade (Fig. 6A). Furthermore, in those Ova/Kb-specific CD8 T cells that did incorporate BrdU during PD-L1 blockade the level of incorporation was reduced (Fig. 6B). Using annexin V staining, no difference in apoptosis was observed between the groups (Fig. 6C). Thus, PD-L1 costimulation operated via enhancement of proliferative pathways.

Bottom Line: However, PD-L1 can also act as a positive costimulator, but the relevant counterreceptor is not known.Simultaneous CD4-T cell depletion and anti-PD-L1 blockade revealed that PD-L1 provided costimulation even in the absence of CD4-T cells.Most importantly, specific blockade of PD-L1 binding to CD80 or to PD-1 did not recapitulate PDL-1 blockade.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, United States of America.

ABSTRACT
Programmed death ligand-1 (PD-L1) is an important negative regulator of T cell immune responses via interactions with PD-1 and CD80. However, PD-L1 can also act as a positive costimulator, but the relevant counterreceptor is not known. We analyzed the role of PD-L1 in CD8-T cell responses to infection with Listeria monocytogenes (LM) or vesicular stomatitis virus (VSV). PD-L1 blockade impaired antigen-specific CD8 effector T cell expansion in response to LM, but not to VSV infection, particularly limiting short-lived effector cell differentiation. Simultaneous CD4-T cell depletion and anti-PD-L1 blockade revealed that PD-L1 provided costimulation even in the absence of CD4-T cells. Most importantly, specific blockade of PD-L1 binding to CD80 or to PD-1 did not recapitulate PDL-1 blockade. The results suggested that PD-L1 plays an important costimulatory role for antigen-specific CD8 T cells during LM infection perhaps through a distinct receptor or interaction epitope.

Show MeSH
Related in: MedlinePlus