The high expression level of programmed death-1 ligand 2 in oral lichen planus and the possible costimulatory effect on human T cells

J Oral Pathol Med. 2011 Aug;40(7):525-32. doi: 10.1111/j.1600-0714.2011.01035.x. Epub 2011 Apr 2.

Abstract

Background: Oral lichen planus (OLP) is a T-cell-mediated chronic autoimmune disease whose precise etiology is unknown. The recently identified costimulatory programmed death-1 (PD-1) molecule and its ligands, PD-L1 and PD-L2, have been identified as CD28-B7 family molecules and constitute a regulatory pathway of potential therapeutic use in immune-mediated diseases.

Methods: We examined the expression of two ligands of PD-1 at both the protein and gene level in the focal mucosa and peripheral blood of OLP patients using immunohistochemistry and real-time PCR. Next, we used the PD-L2.Ig fusion protein and observed its effects on T cells, which were co-cultured with IFN-γ-treated keratinocytes (KCs) in the presence of PHA.

Results: We found that the expression of PD-L2 at both the gene and protein level was statistically different in peripheral blood and local lesion tissue of patients with OLP compared to the normal controls. The proliferation ability of T cells and the expression level of IFN-γ in the supernatant of the above co-culture model were significantly augmented (P < 0.05). PD-L2.Ig fusion protein significantly aggravated the apoptosis of T cells, inhibited the proliferation of T cells and decreased the release levels of IL-2 and IFN-γ in the model (P < 0.05).

Conclusion: These data show that the increased expression of PD-L2, as a costimulatory molecule, may have an important modulatory function on the local immune responses of OLP in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies
  • Antigen Presentation / immunology
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Coloring Agents
  • Epithelium / drug effects
  • Epithelium / immunology
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / analysis
  • Interferon-gamma / pharmacology
  • Interleukin-2 / analysis
  • Keratinocytes / drug effects
  • Keratinocytes / immunology
  • Lichen Planus, Oral / blood
  • Lichen Planus, Oral / immunology*
  • Lymphocyte Activation / immunology*
  • Mouth Mucosa / immunology
  • Phytohemagglutinins / pharmacology
  • Programmed Cell Death 1 Ligand 2 Protein / immunology*
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Antibodies
  • Coloring Agents
  • Interleukin-2
  • PDCD1LG2 protein, human
  • Phytohemagglutinins
  • Programmed Cell Death 1 Ligand 2 Protein
  • Tetrazolium Salts
  • Thiazoles
  • Interferon-gamma
  • thiazolyl blue