Dendritic cells loaded with FK506 kill T cells in an antigen-specific manner and prevent autoimmunity in vivo.
| Publication Type | Academic Article |
| Authors | Orange D, Blachere N, Fak J, Parveen S, Frank M, Herre M, Tian S, Monette S, Darnell R |
| Journal | Elife |
| Volume | 2 |
| Pagination | e00105 |
| Date Published | 02/05/2013 |
| ISSN | 2050-084X |
| Keywords | Antigens, Arthritis, Experimental, Autoimmunity, Calcineurin Inhibitors, Collagen Type II, Dendritic Cells, Drug Delivery Systems, Immunosuppressive Agents, T-Lymphocytes, Tacrolimus |
| 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.DOI:http://dx.doi.org/10.7554/eLife.00105.001. |
| DOI | 10.7554/eLife.00105 |
| PubMed ID | 23390586 |
| PubMed Central ID | PMC3564474 |