Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans
Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans
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DOI：
10.1016/j.humimm.2004.05.016
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发表时间：
2005-01-01
期刊：
影响因子：
2.7
通讯作者：
Toes, REM
中科院分区：
文献类型：
--
作者：
Morgan, ME;van Bilsen, JHM;Toes, REM
转录因子 Foxp3（叉头盒 P3）的表达被认为是小鼠 CD25(+) T 调节细胞功能的关键元件。然而，有关人类 T 调节细胞中 FOXP3 表达的类似参与的文献有限。我们发现，与小鼠细胞不同，FOXP3 mRNA 表达可以在人 CD25(-) 和 CD8(+) 外周血单核细胞中诱导表达，这些细胞在分离后均为 FOXP3 mRNA 表达阴性。刺激后 24-40 小时，FOXP3 mRNA 就开始表达，这表明人类细胞中的激活与 FOXP3 mRNA 表达之间存在相关性。为了确定 FOXP3 表达是否仅限于具有调节表型的 CD4(+)CD25(+) T 细胞，我们分析了几个具有不同特异性的明确 T 细胞克隆和系。令人惊讶的是，在所有克隆中均检测到 FOXP3 mRNA 的表达，并且仅限于 CD25(hi) 群体。尽管如此，CD25(hi)部分并未表现出调节特性，因为CD25(hi)和CD25(低)群体在抗原刺激后表现出相似的增殖和干扰素γ分泌潜力。这些结果表明，与小鼠不同，人类中的 FOXP3 表达可能对具有调节表型的细胞不具有特异性，并且可能只是激活状态的结果。人类免疫学 66, 13-20 (2005)。 (C) 美国组织相容性和免疫遗传学学会，2005 年。由 Elsevier Inc. 出版。
Expression of the transcription factor Foxp3 (forkhead box P3) has been implicated as a key element for CD25(+) T regulatory cell function in mice. However, literature over similar involvement of FOXP3 expression in human T regulatory cells is limited. We found that, unlike murine cells, FOXP3 mRNA expression could be induced in human CD25(-) and CD8(+) peripheral blood mononuclear cells, which were both negative for FOXP3 mRNA expression after isolation. Expression of FOXP3 mRNA began as soon as 24-40 hours after stimulation, demonstrating a correlation between activation and FOXP3 mRNA expression in human cells. In order to determine whether FOXP3 expression is confined to CD4(+)CD25(+) T cells with a regulatory phenotype, we analyzed several well-defined T-cell clones and lines with various specificities. Surprisingly, expression of FOXP3 mRNA was detected in all clones and limited to the CD25(hi) populations. Nonetheless, the CD25(hi) fraction did not display regulatory properties because both the CD25(hi) and CD25(low) populations exhibited a similar proliferative- and interferon-gamma-secreting potential after antigenic stimulation. These results indicate that FOXP3 expression in humans, unlike mice, may not be specific for cells with a regulatory phenotype and may be only a consequence of activation status. Human Immunology 66, 13-20 (2005). (C) American Society for Histocompatibility and Immunogenetics, 2005. Published by Elsevier Inc.