| Autor: |
Zorn, Emmanuel, Nelson, Erik A., Mohseni, Mehrdad, Porcheray, Fabrice, Kim, Haesook, Litsa, Despina, Bellucci, Roberto, Raderschall, Elke, Canning, Christine, Soiffer, Robert J., Frank, David A., Ritz, Jerome |
| Zdroj: |
Blood; September 2006, Vol. 108 Issue: 5 p1571-1579, 9p |
| Abstrakt: |
IL-2 plays a critical role in the maintenance of CD4+CD25+FOXP3+regulatory T cells (Tregs) in vivo. We examined the effects of IL-2 signaling in human Tregs. In vitro, IL-2 selectively up-regulated the expression of FOXP3in purified CD4+CD25+T cells but not in CD4+CD25-cells. This regulation involved the binding of STAT3 and STAT5 proteins to a highly conserved STAT-binding site located in the first intron of the FOXP3gene. We also examined the effects of low-dose IL-2 treatment in 12 patients with metastatic cancer and 9 patients with chronic myelogenous leukemia after allogeneic hematopoietic stem cell transplantation. Overall, IL-2 treatment resulted in a 1.9 median fold increase in the frequency of CD4+CD25+cells in peripheral blood as well as a 9.7 median fold increase in FOXP3expression in CD3+T cells. CD56+CD3-natural killer (NK) cells also expanded during IL-2 therapy but did not express FOXP3.In vitro treatment of NK cells with 5-aza-2′-deoxycytidine restored the IL-2 signaling pathway leading to FOXP3expression, suggesting that this gene was constitutively repressed by DNA methylation in these cells. Our findings support the clinical evaluation of low-dose IL-2 to selectively modulate CD4+CD25+Tregs and increase expression of FOXP3in vivo. |
| Databáze: |
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