Increased Response of Human T-Lymphocytes by Dendritic Cells Pulsed with HPV16E7 and Pleurotus sajor-caju-β-glucan (PBG)

Iran J Immunol. 2018 Dec;15(4):246-255. doi: 10.22034/IJI.2018.39394.

Abstract

Background: Infection with human papillomavirus type 16 (HPV-16) is known to cause cervical cancer, hence the several HPV therapeutic vaccines are developed in E7 oncoproteins and targeted on cell-mediated immunity. Human dendritic cells (HuDCs) are extensively employed in HPV therapeutic vaccines as the carrier or platform for inducing adaptive immune responses. However, the immunomodulators need to be further investigated for vaccine effects. Gray oyster mushroom (Pleurotus sajor-caju) containing β-glucans is a potent immunomodulator with potential to be used in vaccines.

Objective: To study the effect of Pleurotus sajor-caju-β-glucan Polysaccharides (PBG) on human T-lymphocytes by use of the HuDCs' antigen presentation platform for HPV16 vaccine.

Methods: The HPV16-E7 recombinant proteins were constructed in E. Coli. HuDCs pulsed with E7 peptide were cocultured with the T-lymphocytes treated with and without PBG. The number of T-lymphocytes(CD4; CD8) was detected by flowcytometry, and the viral response of T-lymphocytes was measured via IFN-γ release.

Results: The PBG treated group of T-lymphocytes cocultured with the HuDCs pulsed by the HPV16-E7 proteins showed significantly higher numbers of T-lymphocytes and IFN-γ release compared with T-lymphocytes without PBG in vitro. Moreover, a significant improvement in the level of specific IgG neutralizing antibodies to HPV was found in a murine model. Further observed was an increase in the expansion of helper and cytotoxic T-cells and IFN-γ releases in human system.

Conclusion: PBG treatment of T-lymphocytes could be a useful option for prophylactic and therapeutic vaccines in cervical cancer.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Antigen Presentation
  • Antigens, Fungal / immunology*
  • Cancer Vaccines / immunology*
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Female
  • Human papillomavirus 16 / immunology*
  • Humans
  • Immunologic Factors / immunology*
  • Interferon-gamma / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Papillomavirus E7 Proteins / immunology
  • Papillomavirus E7 Proteins / metabolism
  • Papillomavirus Infections / immunology*
  • Papillomavirus Vaccines / immunology*
  • Peptides / immunology
  • Peptides / metabolism
  • Pleurotus / immunology*
  • T-Lymphocytes / immunology*
  • Uterine Cervical Neoplasms / immunology*
  • beta-Glucans / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Fungal
  • Cancer Vaccines
  • Immunologic Factors
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Peptides
  • beta-Glucans
  • oncogene protein E7, Human papillomavirus type 16
  • Interferon-gamma