TY - JOUR TI - Dendritic cells loaded with FK506 kill T cells in an antigen-specific manner and prevent autoimmunity in vivo AU - Orange, Dana E AU - Blachere, Nathalie E AU - Fak, John AU - Parveen, Salina AU - Frank, Mayu O AU - Herre, Margo AU - Tian, Suyan AU - Monette, Sebastien AU - Darnell, Robert B A2 - Glass, Christopher VL - 2 PY - 2013 DA - 2013/02/05 SP - e00105 C1 - eLife 2013;2:e00105 DO - 10.7554/eLife.00105 UR - https://doi.org/10.7554/eLife.00105 AB - 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. KW - dendritic cell KW - rheumatoid arthritis KW - autoimmunity KW - drug delivery KW - FK506 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -