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Mol Ther. 2014 Jul;22(7):1388-1395. doi: 10.1038/mt.2014.50. Epub 2014 Apr 1.

Ultra-low dose interleukin-2 promotes immune-modulating function of regulatory T cells and natural killer cells in healthy volunteers.

Author information

1
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: S.I.itos2@mail.nih.gov.
2
Children's National Health System and The George Washington University, Washington, District of Columbia, USA.
3
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
4
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA; Current address: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
5
Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, Maryland, USA.
6
Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, Maryland, USA; Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA; Current address: Research Branch, Sidra Medical and Research Centre, Doha, Qatar.
7
Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, Maryland, USA; Current address: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
8
Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, Maryland, USA; Current address: Research Branch, Sidra Medical and Research Centre, Doha, Qatar.
9
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA; Current address: Department of Hematology, Clinical Immunology and Infectious Disease, Ehime University, Ehime, Japan.
10
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA; Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, Maryland, USA; Current address: Alaska Native Tribal Health Consortium, Anchorage, Alaska, USA.
11
Pharmacy Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
12
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA; Trans-NIH Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

Low-dose interleukin-2 (IL-2) expands regulatory T cells (Tregs) 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 Tregs 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 Tregs with increased suppressive function. There was a marked expansion of CD56(bright) NK cells with enhanced interferon-γ (IFN-γ) production. Serum cytokine profiling demonstrated increase of IFN-γ 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.

PMID:
24686272
PMCID:
PMC4089007
DOI:
10.1038/mt.2014.50
[Indexed for MEDLINE]
Free PMC Article

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