Journal
MOLECULAR THERAPY
Volume 22, Issue 7, Pages 1388-1395Publisher
CELL PRESS
DOI: 10.1038/mt.2014.50
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Funding
- National Institutes of Health, National Heart, Lung, and Blood Institute
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Low-dose interleukin-2 (IL-2) expands regulatory T cells (T-regs) and natural killer (NK) cells after stem cell transplantation (SCT) and may reduce graft-versus-host disease (GVHD). We hypothesized that ultra-low dose (ULD) IL-2 could serve as an immune-modulating agent for stem cell donors to prevent GVHD following SCT. However, the safety, dose level, and immune signatures of ULD IL-2 in immune-competent healthy subjects remain unknown. Here, we have characterized the phenotype and function of T-regs and NK cells as well as the gene expression and cytokine profiles of 21 healthy volunteers receiving 50,000 to 200,000 units/m(2)/day IL-2 for 5 days. ULD IL-2 was well tolerated and induced a significant increase in the frequency of T-regs with increased suppressive function. There was a marked expansion of CD56(bright) NK cells with enhanced interferon-gamma (IFN-gamma) production. Serum cytokine profiling demonstrated increase of IFN-gamma induced protein 10 (IP-10). Gene expression analysis revealed significant changes in a highly restricted set of genes, including FOXP3, IL-2RA, and CISH. This is the first study to evaluate global immune-modulating function of ULD IL-2 in healthy subjects and to support the future studies administrating ULD IL-2 to stem cell donors.
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