Abe Masaki, Uchihashi Kinya, Kazuto Tsuruda, Osaka Akemi, Yanagihara Katsunori, Tsukasaki Kunihiro, Hasegawa Hiroo, Yamada Yasuaki, Kamihira Shimeru
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Eur J Haematol. 2008 Sep;81(3):209-17. doi: 10.1111/j.1600-0609.2008.01105.x. Epub 2008 May 27.
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.
Foxp3是调节性T细胞（Treg细胞）的主控基因，Treg细胞是主要表达CD25的CD4(+) T细胞的一个新亚群。我们在此利用健康对照（HC）、1型人类T细胞白血病病毒（HTLV-1）感染的无症状携带者（AC）、成人T细胞白血病（ATL）患者的外周血样本以及各种造血细胞系，描述正常和白血病CD4(+)CD25(+) T细胞之间Foxp3表达谱的不同特征。健康对照中大多数CD4(+)CD25(+) T细胞Foxp3呈阳性，但无症状携带者中的CD4(+)CD25(+) T细胞并非全部呈阳性，这表明在正常T细胞中Foxp3表达并不总是与CD25表达相关联。持续表达CD25的白血病（ATL）T细胞具有Foxp3表达异质性的特征，如病例内和病例间强度的异质性、与CD25表达不一致以及mRNA及其蛋白表达的差异。令人惊讶的是，即使在大多数不表达CD25的细胞系中也能检测到可识别量的Foxp3 mRNA，其中一小部分Foxp3蛋白呈阳性。Foxp3在HTLV-1感染细胞系中的亚细胞定位主要在细胞质中，这与原发性ATL细胞不同。这些发现表明Foxp3有两个方面：Treg细胞的基本特征以及肿瘤发生继发的分子模拟。总之，正常T细胞中的Foxp3而非mRNA，在从CD25(+) T细胞群体中区分出一部分Treg细胞方面基本有效，而白血病T细胞中Foxp3表达的调节可能与肿瘤发生有关，并且具有潜在的临床应用价值。
