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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, Lefrançois 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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PD-L1 induction in response to infection.A, PD-L1 expression on CD4 T, CD8 T, and B cells on day 2 after LM or VSV infection. Filled histogram: naive control. Open histogram: day 2 after LM or VSV i.v. infection. B, Comparison of PD-L1 expression on total CD8 T cells 2 days after LM or VSV infection. C, Comparison of PD-L1 expression by naïve (CD11alow) and activated/memory (CD11ahigh) CD8 T cells and representative 2-D plot of CD11a versus PD-L1 expression. Data were analyzed by Student's t test. (***p<0.001). Gating strategy for T cells is based on CD4, CD8 and CD3 expression. Data are representative of three independent experiments with five mice per group.
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pone-0056539-g001: PD-L1 induction in response to infection.A, PD-L1 expression on CD4 T, CD8 T, and B cells on day 2 after LM or VSV infection. Filled histogram: naive control. Open histogram: day 2 after LM or VSV i.v. infection. B, Comparison of PD-L1 expression on total CD8 T cells 2 days after LM or VSV infection. C, Comparison of PD-L1 expression by naïve (CD11alow) and activated/memory (CD11ahigh) CD8 T cells and representative 2-D plot of CD11a versus PD-L1 expression. Data were analyzed by Student's t test. (***p<0.001). Gating strategy for T cells is based on CD4, CD8 and CD3 expression. Data are representative of three independent experiments with five mice per group.

Mentions: We examined PD-L1 expression after i.v. infection with LM-ova or VSV-ova. Two days after infection with either pathogen, PD-L1 was markedly upregulated on bulk CD4 T cells, CD8 T cells, and B cells (Fig.1A). PD-L1 expression on CD8 T cells peaked ∼day 2 post-infection and subsequently declined (Fig. 1B). LM infection induced higher levels of PD-L1 on bulk CD8 T cells as compared to levels induced by VSV infection (Fig. 1B). Moreover, CD11ahigh effector/memory phenotype CD8 T cells expressed substantially more PD-L1 as compared to their CD11alow naïve counterparts (Fig. 1C). Indeed, high PD-L1 expression correlated with high CD11a levels (Fig. 1C). Thus, PD-L1 expression was transiently upregulated on T cells after LM infection, similar to other costimulatory molecules [19], [20].


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, Lefrançois L - PLoS ONE (2013)

PD-L1 induction in response to infection.A, PD-L1 expression on CD4 T, CD8 T, and B cells on day 2 after LM or VSV infection. Filled histogram: naive control. Open histogram: day 2 after LM or VSV i.v. infection. B, Comparison of PD-L1 expression on total CD8 T cells 2 days after LM or VSV infection. C, Comparison of PD-L1 expression by naïve (CD11alow) and activated/memory (CD11ahigh) CD8 T cells and representative 2-D plot of CD11a versus PD-L1 expression. Data were analyzed by Student's t test. (***p<0.001). Gating strategy for T cells is based on CD4, CD8 and CD3 expression. 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-g001: PD-L1 induction in response to infection.A, PD-L1 expression on CD4 T, CD8 T, and B cells on day 2 after LM or VSV infection. Filled histogram: naive control. Open histogram: day 2 after LM or VSV i.v. infection. B, Comparison of PD-L1 expression on total CD8 T cells 2 days after LM or VSV infection. C, Comparison of PD-L1 expression by naïve (CD11alow) and activated/memory (CD11ahigh) CD8 T cells and representative 2-D plot of CD11a versus PD-L1 expression. Data were analyzed by Student's t test. (***p<0.001). Gating strategy for T cells is based on CD4, CD8 and CD3 expression. Data are representative of three independent experiments with five mice per group.
Mentions: We examined PD-L1 expression after i.v. infection with LM-ova or VSV-ova. Two days after infection with either pathogen, PD-L1 was markedly upregulated on bulk CD4 T cells, CD8 T cells, and B cells (Fig.1A). PD-L1 expression on CD8 T cells peaked ∼day 2 post-infection and subsequently declined (Fig. 1B). LM infection induced higher levels of PD-L1 on bulk CD8 T cells as compared to levels induced by VSV infection (Fig. 1B). Moreover, CD11ahigh effector/memory phenotype CD8 T cells expressed substantially more PD-L1 as compared to their CD11alow naïve counterparts (Fig. 1C). Indeed, high PD-L1 expression correlated with high CD11a levels (Fig. 1C). Thus, PD-L1 expression was transiently upregulated on T cells after LM infection, similar to other costimulatory molecules [19], [20].

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