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