4.8 Article

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

Journal

ELIFE
Volume 2, Issue -, Pages -

Publisher

ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.00105

Keywords

-

Categories

Funding

  1. Howard Hughes Medical Institute
  2. National Institutes of Health [R01 CA093507]
  3. American College of Rheumatology REF Physician Scientist Development Award
  4. Rockefeller University Hospital CTSA [UL1RR024143, 8 KL2 TR000151]
  5. Beth and Ravenel Curry clinical scholarship

Ask authors/readers for more resources

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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available