Title | Dendritic cells loaded with FK506 kill T cells in an antigen-specific manner and prevent autoimmunity in vivo. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Orange DE, Blachere NE, Fak J, Parveen S, Frank MO, Herre M, Tian S, Monette S, Darnell RB |
Journal | Elife |
Volume | 2 |
Pagination | e00105 |
Date Published | 2013 Feb 05 |
ISSN | 2050-084X |
Keywords | Animals, Antigens, Arthritis, Experimental, Autoimmunity, Calcineurin Inhibitors, Cells, Cultured, Coculture Techniques, Collagen Type II, Dendritic Cells, Diffusion, Drug Delivery Systems, Humans, Immunosuppressive Agents, Lymphocyte Activation, Male, Mice, Inbred DBA, T-Lymphocytes, Tacrolimus, Time Factors |
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 |
Alternate Journal | Elife |
PubMed ID | 23390586 |
PubMed Central ID | PMC3564474 |
Grant List | KL2 TR000151 / TR / NCATS NIH HHS / United States UL1 RR024143 / RR / NCRR NIH HHS / United States R01 CA093507 / CA / NCI NIH HHS / United States |
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