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PD-1 inhibits antiviral immunity at the effector phase in the liver.

Iwai Y, Terawaki S, Ikegawa M, Okazaki T, Honjo T - J. Exp. Med. (2003)

Bottom Line: Here we report that PD-L1, the ligand for the immunoinhibitory receptor PD-1, was expressed on vascular endothelium in peripheral tissues.The absence of PD-1 induced proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus.These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.

ABSTRACT
Unlike naive T cells, effector T cells can be activated by either T cell receptor signal or costimulatory signal alone and therefore the absence of costimulatory molecules on tissue cells cannot explain the tolerance mechanism at the effector phase. Here we report that PD-L1, the ligand for the immunoinhibitory receptor PD-1, was expressed on vascular endothelium in peripheral tissues. Liver nonparenchymal cells including sinusoidal endothelial cells and Kupffer cells constitutively expressed PD-L1 and inhibited proliferation and cell division of activated T cells expressing PD-1. The absence of PD-1 induced proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus. These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity.

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PD-L1 expression on liver nonparenchymal cells. (a) Cryosections of murine liver were stained with anti-ICAM-1 (top, green) or anti-PD-L1 (bottom, green). Nuclei were counterstained with propidium iodide (red). CV, central vein. Original magnification, ×40. (b) Surface phenotype of Kupffer cells and LSECs. LNPCs were isolated from murine livers and stained with anti-CD54 (ICAM-1)-FITC and anti-CD11b-APC, in combination with biotinylated mAb for ICAM-1, PD-L1, B7–1, or B7–2, followed by streptavidin-PE. Kupffer cells and LSECs were gated as CD54+CD11bhigh and CD54+CD11blow cells, respectively.
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fig2: PD-L1 expression on liver nonparenchymal cells. (a) Cryosections of murine liver were stained with anti-ICAM-1 (top, green) or anti-PD-L1 (bottom, green). Nuclei were counterstained with propidium iodide (red). CV, central vein. Original magnification, ×40. (b) Surface phenotype of Kupffer cells and LSECs. LNPCs were isolated from murine livers and stained with anti-CD54 (ICAM-1)-FITC and anti-CD11b-APC, in combination with biotinylated mAb for ICAM-1, PD-L1, B7–1, or B7–2, followed by streptavidin-PE. Kupffer cells and LSECs were gated as CD54+CD11bhigh and CD54+CD11blow cells, respectively.

Mentions: We examined PD-L1 expression in the liver by immunohistochemistry using the anti-PD-L1 mAb (Fig. 2 a). PD-L1 staining was similar to that of ICAM-1 (CD54), which is expressed on LNPCs including Kupffer cells and LSECs (Fig. 2 a). To confirm the PD-L1 expression in the liver, LNPCs were isolated and analyzed by flow cytometry (Fig. 2 b). LNPCs consisted of CD54+CD11blow LSECs (75–80%) and CD54+CD11bhigh Kupffer cells (20–25%). Kupffer cells coexpressed PD-L1 with B7–1, B7–2, and ICAM-1. The expression of PD-L1 on LSECs was weak but significant as compared with that of B7–1 or B7–2. Neither LSECs nor Kupffer cells expressed PD-L2.


PD-1 inhibits antiviral immunity at the effector phase in the liver.

Iwai Y, Terawaki S, Ikegawa M, Okazaki T, Honjo T - J. Exp. Med. (2003)

PD-L1 expression on liver nonparenchymal cells. (a) Cryosections of murine liver were stained with anti-ICAM-1 (top, green) or anti-PD-L1 (bottom, green). Nuclei were counterstained with propidium iodide (red). CV, central vein. Original magnification, ×40. (b) Surface phenotype of Kupffer cells and LSECs. LNPCs were isolated from murine livers and stained with anti-CD54 (ICAM-1)-FITC and anti-CD11b-APC, in combination with biotinylated mAb for ICAM-1, PD-L1, B7–1, or B7–2, followed by streptavidin-PE. Kupffer cells and LSECs were gated as CD54+CD11bhigh and CD54+CD11blow cells, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196084&req=5

fig2: PD-L1 expression on liver nonparenchymal cells. (a) Cryosections of murine liver were stained with anti-ICAM-1 (top, green) or anti-PD-L1 (bottom, green). Nuclei were counterstained with propidium iodide (red). CV, central vein. Original magnification, ×40. (b) Surface phenotype of Kupffer cells and LSECs. LNPCs were isolated from murine livers and stained with anti-CD54 (ICAM-1)-FITC and anti-CD11b-APC, in combination with biotinylated mAb for ICAM-1, PD-L1, B7–1, or B7–2, followed by streptavidin-PE. Kupffer cells and LSECs were gated as CD54+CD11bhigh and CD54+CD11blow cells, respectively.
Mentions: We examined PD-L1 expression in the liver by immunohistochemistry using the anti-PD-L1 mAb (Fig. 2 a). PD-L1 staining was similar to that of ICAM-1 (CD54), which is expressed on LNPCs including Kupffer cells and LSECs (Fig. 2 a). To confirm the PD-L1 expression in the liver, LNPCs were isolated and analyzed by flow cytometry (Fig. 2 b). LNPCs consisted of CD54+CD11blow LSECs (75–80%) and CD54+CD11bhigh Kupffer cells (20–25%). Kupffer cells coexpressed PD-L1 with B7–1, B7–2, and ICAM-1. The expression of PD-L1 on LSECs was weak but significant as compared with that of B7–1 or B7–2. Neither LSECs nor Kupffer cells expressed PD-L2.

Bottom Line: Here we report that PD-L1, the ligand for the immunoinhibitory receptor PD-1, was expressed on vascular endothelium in peripheral tissues.The absence of PD-1 induced proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus.These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.

ABSTRACT
Unlike naive T cells, effector T cells can be activated by either T cell receptor signal or costimulatory signal alone and therefore the absence of costimulatory molecules on tissue cells cannot explain the tolerance mechanism at the effector phase. Here we report that PD-L1, the ligand for the immunoinhibitory receptor PD-1, was expressed on vascular endothelium in peripheral tissues. Liver nonparenchymal cells including sinusoidal endothelial cells and Kupffer cells constitutively expressed PD-L1 and inhibited proliferation and cell division of activated T cells expressing PD-1. The absence of PD-1 induced proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus. These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity.

Show MeSH
Related in: MedlinePlus