Induction of T cell anergy by liposomes with incorporated major histocompatibility complex (MHC) II/peptide complexes.
OBJECTIVE
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.
van Rensen
A J
AJ
Department of Pharmaceutics, Faculty of Pharmacy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Taams
L S
LS
Grosfeld-Stulemeyer
M C
MC
van Eden
W
W
Crommelin
D J
DJ
Wauben
M H
MH
D000818:Animals; D002455:Cell Division / Q000276:immunology; D017635:Clonal Anergy; D015536:Down-Regulation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008081:Liposomes; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D008081:Liposomes; D011948:Receptors, Antigen, T-Cell