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Foxp3 expression on normal and leukemic CD4+CD25+ T cells implicated in human T‐cell leukemia virus type‐1 is inconsistent with Treg cells

Foxp3 is a master gene of Treg cells, a novel subset of CD4+ T cells primarily expressing CD25. We describe here different features in Foxp3 expression profile between normal and leukemic CD4+CD25+ T cells, using peripheral blood samples from healthy controls (HCs), human T‐cell leukemia virus type‐1 (HTLV‐1)‐infected asymptomatic carriers (ACs), patients with adult T‐cell leukemia (ATL), and various hematopoietic cell lines. The majority of CD4+CD25+ T cells in HCs were positive for Foxp3, but not all CD4+CD25+ T cells in ACs were positive, indicating that Foxp3 expression is not always linked to CD25 expression in normal T cells. Leukemic (ATL) T cells constitutively expressing CD25 were characteristic of heterogeneous Foxp3 expression, such as intra‐ and inter‐case heterogeneity in intensity, inconsistency with CD25 expression, and a discrepancy in the mRNA and its protein expression. Surprisingly, a discernible amount of Foxp3 mRNA was detectable even in most cell lines without CD25 expression, a small fraction of which was positive for the Foxp3 proteins. The subcellular localization of Foxp3 in HTLV‐1‐infected cell lines was mainly cytoplasmic, different from that of primary ATL cells. These findings indicate that Foxp3 has two facets: essential Treg identity and molecular mimicry secondary to tumorigenesis. Conclusively, Foxp3 in normal T cells, but not mRNA, is basically potent at discriminating a subset of Treg cells from CD25+ T‐cell populations, whereas the modulation of Foxp3 expression in leukemic T cells could be implicated in oncogenesis and has a potentially useful clinical role.