Research ArticleGraft Vs Host Disease

Low-Dose Interleukin-2 Therapy Restores Regulatory T Cell Homeostasis in Patients with Chronic Graft-Versus-Host Disease

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Science Translational Medicine  03 Apr 2013:
Vol. 5, Issue 179, pp. 179ra43
DOI: 10.1126/scitranslmed.3005265

Restoring Balance to the Immune System

Hematopoietic stem cell transplantation can be a lifesaving therapy for patients with certain types of cancers or other blood disorders. However, it’s rare to find a perfect match, and transplants frequently occur from donors who are antigenically different from the recipient. When this happens, the graft itself can attack the host as foreign tissue, a response called graft-versus-host disease (GVHD). Matsuoka et al. now report that daily low-dose interleukin-2 (IL-2) can expand regulatory T cells (Tregs) and improve chronic GVHD.

The authors studied the effects of daily low-dose IL-2 on different subsets of CD4+ T cells in patients with chronic GVHD. Conventional T cells in these patients had altered phosphorylation of the signaling molecule signal transducer and activator of transcription 5 (Stat5) and a functional deficiency in IL-2. When this IL-2 deficiency was replaced with their therapy, Stat5 phosphorylation levels were selectively increased in Tregs but decreased conventional T cells. Indeed, although daily low-dose IL-2 had minimal effects on conventional T cells, it induced a series of changes to Treg homeostasis that likely led to the establishment of immune tolerance.

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