IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients.
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+ CD25(hi) T cells in immune intact patients with melanoma or renal cancer. We found that the frequency of CD4+ CD25(hi) 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 consistently increased in CD4 T cells following IL-2 treatment. Functional analysis of the increased number of CD4+ CD25(hi) 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+ CD25(hi) 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.
Ahmadzadeh
Mojgan
M
Surgery Branch, NCI, NIH, Bethesda, MD 20892, USA.
Rosenberg
Steven A
SA
D000293:Adolescent; D000328:Adult; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2