Tolerance Induced by Antigen-Loaded PLG Nanoparticles Affects the Phenotype and Trafficking of Transgenic CD4+ and CD8+ T Cells

Cells. 2021 Dec 7;10(12):3445. doi: 10.3390/cells10123445.


We have shown that PLG nanoparticles loaded with peptide antigen can reduce disease in animal models of autoimmunity and in a phase 1/2a clinical trial in celiac patients. Clarifying the mechanisms by which antigen-loaded nanoparticles establish tolerance is key to further adapting them to clinical use. The mechanisms underlying tolerance induction include the expansion of antigen-specific CD4+ regulatory T cells and sequestration of autoreactive cells in the spleen. In this study, we employed nanoparticles loaded with two model peptides, GP33-41 (a CD8 T cell epitope derived from lymphocytic choriomeningitis virus) and OVA323-339 (a CD4 T cell epitope derived from ovalbumin), to modulate the CD8+ and CD4+ T cells from two transgenic mouse strains, P14 and DO11.10, respectively. Firstly, it was found that the injection of P14 mice with particles bearing the MHC I-restricted GP33-41 peptide resulted in the expansion of CD8+ T cells with a regulatory cell phenotype. This correlated with reduced CD4+ T cell viability in ex vivo co-cultures. Secondly, both nanoparticle types were able to sequester transgenic T cells in secondary lymphoid tissue. Flow cytometric analyses showed a reduction in the surface expression of chemokine receptors. Such an effect was more prominently observed in the CD4+ cells rather than the CD8+ cells.

Keywords: cell trafficking; chemokine receptors; nanoparticles; regulatory T cells; tolerance; type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • Antigens / pharmacology
  • Antigens, Viral / immunology
  • Antigens, Viral / pharmacology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Celiac Disease / genetics
  • Celiac Disease / immunology
  • Celiac Disease / therapy*
  • Cell Lineage / drug effects
  • Cell Lineage / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / pharmacology
  • Glycoproteins / immunology
  • Glycoproteins / pharmacology
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / immunology*
  • Mice
  • Mice, Transgenic
  • Nanoparticles / chemistry
  • Ovalbumin / immunology
  • Ovalbumin / pharmacology
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology
  • Peptides / immunology
  • Peptides / pharmacology
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / pharmacology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Viral Proteins / immunology
  • Viral Proteins / pharmacology


  • Antigens
  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Glycoproteins
  • OVA 323-339
  • Peptide Fragments
  • Peptides
  • Viral Proteins
  • glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Ovalbumin