Interleukin-2 and regulatory T cells in graft-versus-host disease

John Koreth, Ken-ichi Matsuoka, Haesook T. Kim, Sean M. McDonough, Bhavjot Bindra, Edwin P. Alyea, Philippe Armand, Corey Cutler, Vincent T. Ho, Nathaniel S. Treister, Don C. Bienfang, Sashank Prasad, Dmitrios Tzachanis, Robin M. Joyce, David E. Avigan, Joseph H. Antin, Jerome Ritz, Robert J. Soiffer

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Abstract

BACKGROUND: Dysfunction of regulatory T (Treg) cells has been detected in diverse inflammatory disorders, including chronic graft-versus-host disease (GVHD). Interleukin-2 is critical for Treg cell growth, survival, and activity. We hypothesized that low-dose interleukin-2 could preferentially enhance Treg cells in vivo and suppress clinical manifestations of chronic GVHD. METHODS: In this observational cohort study, patients with chronic GVHD that was refractory to glucocorticoid therapy received daily low-dose subcutaneous interleukin-2 (0.3×10 6, 1×10 6, or 3×10 6 IU per square meter of body-surface area) for 8 weeks. The end points were safety and clinical and immunologic response. After a 4-week hiatus, patients with a response could receive interleukin-2 for an extended period. RESULTS: A total of 29 patients were enrolled. None had progression of chronic GVHD or relapse of a hematologic cancer. The maximum tolerated dose of interleukin-2 was 1×106 IU per square meter. The highest dose level induced unacceptable constitutional symptoms. Of the 23 patients who could be evaluated for response, 12 had major responses involving multiple sites. The numbers of CD4+ Treg cells were preferentially increased in all patients, with a peak median value, at 4 weeks, that was more than eight times the baseline value (P

Original languageEnglish
Pages (from-to)2055-2066
Number of pages12
JournalNew England Journal of Medicine
Volume365
Issue number22
Publication statusPublished - Dec 1 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Koreth, J., Matsuoka, K., Kim, H. T., McDonough, S. M., Bindra, B., Alyea, E. P., Armand, P., Cutler, C., Ho, V. T., Treister, N. S., Bienfang, D. C., Prasad, S., Tzachanis, D., Joyce, R. M., Avigan, D. E., Antin, J. H., Ritz, J., & Soiffer, R. J. (2011). Interleukin-2 and regulatory T cells in graft-versus-host disease. New England Journal of Medicine, 365(22), 2055-2066.