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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2409-2414.
Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-06-2399.


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Submitted June 16, 2005
Accepted October 30, 2005

IL-2 Administration Increases CD4+CD25hiFoxp3+ Regulatory T Cells in Cancer Patients

Mojgan Ahmadzadeh and Steven A Rosenberg*

National Institutes of Health, Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA

* Corresponding author; email: sar{at}nih.gov.

Interleukin-2 (IL-2) is historically known as a T cell growth factor. Accumulating evidence from knockout mice suggests that IL-2 is crucial for the homeostasis and function of CD4+CD25+ regulatory T cells in vivo. However, the impact of administered IL-2 in an immune intact host has not been studied in rodents or humans. Here, we studied the impact of IL-2 administration on the frequency and function of human CD4+CD25hi T cells in immune intact patients with melanoma or renal cancer. We found that the frequency of CD4+CD25hi T cells was significantly increased after IL-2 treatment, and these cells expressed phenotypic markers associated with regulatory T cells. In addition, both transcript and protein levels of Foxp3, a transcription factor exclusively expressed on regulatory T cells, were also consistently increased in purified CD4 T cells following IL-2 treatment. Functional analysis of the increased number of CD4+CD25hi T cells revealed that this population exhibited potent suppressive activity in vitro. Collectively, our results demonstrate that administration of high dose IL-2 increased the frequency of circulating CD4+CD25hi Foxp3+ regulatory T cells. Our findings suggest that selective inhibition of IL-2 mediated enhancement of regulatory T cells may improve the therapeutic effectiveness of IL-2 administration.


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