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Dendritic cells loaded with FK506 kill T cells in an antigen-specific manner and prevent autoimmunity in vivo

Authors :
Dana E Orange
Nathalie E Blachere
John Fak
Salina Parveen
Mayu O Frank
Margo Herre
Suyan Tian
Sebastien Monette
Robert B Darnell
Source :
eLife, Vol 2 (2013)
Publication Year :
2013
Publisher :
eLife Sciences Publications Ltd, 2013.

Abstract

FK506 (Tacrolimus) is a potent inhibitor of calcineurin that blocks IL2 production and is widely used to prevent transplant rejection and treat autoimmunity. FK506 treatment of dendritic cells (FKDC) limits their capacity to stimulate T cell responses. FK506 does not prevent DC survival, maturation, or costimulatory molecule expression, suggesting that the limited capacity of FKDC to stimulate T cells may be due to inhibition of calcineurin signaling in the DC. Instead, we demonstrate that DC inhibit T cells by sequestering FK506 and continuously releasing the drug over several days. T cells encountering FKDC proliferate but fail to upregulate the survival factor bcl-xl and die, and IL2 restores both bcl-xl and survival. In mice, FKDC act in an antigen-specific manner to inhibit T-cell mediated autoimmune arthritis. This establishes that DCs can act as a cellular drug delivery system to target antigen specific T cells.

Details

Language :
English
ISSN :
2050084X
Volume :
2
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.57e30b8857974b23891086e060e84db5
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.00105