Yamamoto Mayuko, Tsuji-Takayama Kazue, Suzuki Motoyuki, Harashima Akira, Sugimoto Akira, Motoda Ryuichi, Yamasaki Fumiyuki, Nakamura Shuji, Kibata Masayoshi
Cell Biology Institute, Research Center, Hayashibara Biochemical Laboratories Inc., 675-1 Fujisaki, Okayama 702-8006, Japan.
Leuk Res. 2008 Apr;32(4):651-8. doi: 10.1016/j.leukres.2007.08.020. Epub 2007 Oct 24.
Studies of FOXP3 expression have thus far focused on T cells, including both normal and malignant T cells. In particular, adult T cell leukemia/lymphoma (ATLL) cells have been studied intensively because their phenotype resembles that of normal CD4(+)CD25(+) regulatory T (Treg) cells. However, a comprehensive study of FOXP3 expression covering all hematopoietic cell lineages has not yet been performed. In this study, FOXP3 mRNA expression was examined by quantitative PCR using a large collection of human hematopoietic cell lines derived from leukemia/lymphoma or virus-transformation, including cells lines with T, B, plasmacytoid, myeloid, monocytic, megakaryocytic, erythroid, and NK lineages. Unexpectedly, we found FOXP3 mRNA expression in a number of cell lines belonging to all of the cell lineages investigated. In sharp contrast, FOXP3 protein expression was found in only three cell lines, all of which were HTLV-I-infected. Several non-T cell lines expressed higher levels of mRNA but were still negative for protein expression. The broad mRNA expression contrasts with the restricted protein expression of FOXP3 in human hematopoietic cell lines, suggesting that post-transcriptional control mechanisms may control FOXP3 protein expression.
迄今为止,对FOXP3表达的研究主要集中在T细胞,包括正常和恶性T细胞。特别是,成人T细胞白血病/淋巴瘤(ATLL)细胞已被深入研究,因为它们的表型与正常CD4(+)CD25(+)调节性T(Treg)细胞相似。然而,尚未对涵盖所有造血细胞谱系的FOXP3表达进行全面研究。在本研究中,使用大量源自白血病/淋巴瘤或病毒转化的人类造血细胞系,包括具有T、B、浆细胞样、髓样、单核细胞、巨核细胞、红系和NK谱系的细胞系,通过定量PCR检测FOXP3 mRNA表达。出乎意料的是,我们在属于所有研究细胞谱系的许多细胞系中发现了FOXP3 mRNA表达。与之形成鲜明对比的是,仅在三个细胞系中发现了FOXP3蛋白表达,所有这些细胞系均感染了HTLV-I。几个非T细胞系表达了更高水平的mRNA,但蛋白表达仍为阴性。FOXP3在人类造血细胞系中的mRNA广泛表达与蛋白表达受限形成对比,表明转录后控制机制可能控制FOXP3蛋白表达。