Induction of T cell anergy by liposomes with incorporated major histocompatibility complex (MHC) II/peptide complexes

Pharm Res. 2000 Jun;17(6):720-6. doi: 10.1023/a:1007586400631.

Abstract

Purpose: The aim of this study was to use small unilamellar liposomes with incorporated MHC II/peptide complexes as a carrier system for multivalent antigen presentation to CD4 + T cells.

Methods: Purified peptide pre-loaded MHC II molecules were incorporated into small unilamellar liposomes and tested for their ability to activate A2b T cells. The outcome of T cell activation by such liposomes in the absence of accessory cells was tested via flow cytometry and a T cell anergy assay.

Results: Provided the presence of external co-stimulation, MHC II/ peptide liposomes were able to induce proliferation of the A2b T cell clone. More importantly incubation of these T cells with MHC II/ peptide liposomes in the absence of co-stimulation did not induce proliferation, however, a MHC/peptide ligand-density dependent down-regulation of the TCR was observed. Interestingly, when T cells after incubation with the MHC II/peptide liposomes were restimulated with their specific antigen in the presence of professional APC, these cells were anergic.

Conclusions: We propose MHC II/peptide liposomes as a novel means to induce T cell anergy. The possibility to prepare 'tailor-made' liposomal formulations may provide liposomes with an important advantage for applications in immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / immunology
  • Clonal Anergy*
  • Down-Regulation
  • Histocompatibility Antigens Class II / immunology*
  • Liposomes*
  • Rats
  • Rats, Inbred Lew
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Histocompatibility Antigens Class II
  • Liposomes
  • Receptors, Antigen, T-Cell