| Literature DB >> 24686272 |
Sawa Ito1, Catherine M Bollard2, Mattias Carlsten3, Jan Joseph Melenhorst4, Angélique Biancotto5, Ena Wang6, Jinguo Chen5, Yuri Kotliarov5, Foo Cheung5, Zhi Xie7, Francesco Marincola8, Kazushi Tanimoto9, Minoo Battiwalla3, Matthew J Olnes10, Shira Perl5, Paula Schum5, Thomas E Hughes11, Keyvan Keyvanfar3, Nancy Hensel3, Pawel Muranski3, Neal S Young12, A John Barrett3.
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.Entities:
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Year: 2014 PMID： 24686272 PMCID： PMC4089007 DOI： 10.1038/mt.2014.50
Source DB: PubMed Journal: Mol Ther ISSN： 1525-0016 Impact factor: 11.454