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.
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Masaki
M
Abe
Kinya
K
Uchihashi
Tsuruda
T
Kazuto
Akemi
A
Osaka
Katsunori
K
Yanagihara
Kunihiro
K
Tsukasaki
Hiroo
H
Hasegawa
Yasuaki
Y
Yamada
Shimeru
S
Kamihira
D015153:Blotting, Western; D002460:Cell Line; D005434:Flow Cytometry / Q000379:methods; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D020869:Gene Expression Profiling; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology* / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger