In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 5, No. 179 ( 2013-04-03)
Abstract:
CD4 + Foxp3 + regulatory T cells (T regs ) play a central role in the maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation. We recently reported that daily administration of low-dose interleukin-2 (IL-2) induces selective expansion of functional T regs and clinical improvement of chronic graft-versus-host disease (GVHD). To define the mechanisms of action of IL-2 therapy, we examined the immunologic effects of this treatment on homeostasis of CD4 + T cell subsets after transplant. We first demonstrated that chronic GVHD is characterized by constitutive phosphorylation of signal transducer and activator of transcription 5 (Stat5) in conventional CD4 + T cells (T cons ) associated with elevated amounts of IL-7 and IL-15 and relative functional deficiency of IL-2. IL-2 therapy resulted in the selective increase of Stat5 phosphorylation in T regs and a decrease of phosphorylated Stat5 in T cons . Over an 8-week period, IL-2 therapy induced a series of changes in T reg homeostasis, including increased proliferation, increased thymic export, and enhanced resistance to apoptosis. Low-dose IL-2 had minimal effects on T cons . These findings define the mechanisms whereby low-dose IL-2 therapy restores the homeostasis of CD4 + T cell subsets and promotes the reestablishment of immune tolerance.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.3005265
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2013