Human CD4+CD25+Foxp3+ Regulatory T Cells Do Not Constitutively Express IL-35
Human CD4+CD25+Foxp3+ Regulatory T Cells Do Not Constitutively Express IL-35
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DOI：
10.4049/jimmunol.181.10.6898
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发表时间：
2008-11-15
影响因子：
4.4
通讯作者：
Devergne, Odile
中科院分区：
文献类型：
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作者：
Bardel, Emilie;Larousserie, Frederique;Devergne, Odile
ebv诱导的基因3 （EB13）可以与p28结合形成异二聚体细胞因子IL-27，或与IL-12的p35亚基结合形成EB13/p35异二聚体，最近被命名为IL-35。在小鼠中，IL-35已被证明在CD4(+)CD25(+)Foxp3（+）调节性T细胞（Treg细胞）中组成性表达，并被认为有助于它们的抑制活性。在这项研究中，我们研究了人类Treg细胞是否表达il -35。人胸腺双染色分析显示，Foxp3（+）和CD25（+）细胞均不共表达EB13。同样，存在于人类淋巴结、扁桃体、脾脏和肠道中的Foxp3（+）细胞也不表达EB13。与这些原位观察结果一致，从血液或扁桃体中纯化的Treg细胞通过免疫印迹法对EB13呈阴性。其他人类T细胞亚群，包括效应T细胞、初始和记忆CD4(+) T细胞、CD8（+）和γ δ T细胞也不组成性地表达EB13，这与小鼠CD8（+）和γ δ T细胞中观察到的IL-35表达形成对比。此外，尽管CD3/CD28刺激在各种CD4(+) T细胞亚群中持续诱导低水平的EB13，但在CD3/CD28刺激的Treg细胞中未检测到EB13。RT-PCR分析显示，Teff细胞和Treg细胞中均检测到p35转录本，而EB13转录本仅在活化的Teff细胞中检测到，而在静息细胞和活化的Treg细胞中均未检测到。因此，与小鼠相比，人类Treg细胞不表达可检测量的IL-35。中华免疫学杂志，2008,18(1):698 -6905。
EBV-induced gene 3 (EB13) can associate with p28 to form the heterodimeric cytokine IL-27, or with the p35 subunit of IL-12 to form the EB13/p35 heterodimer, recently named IL-35. In mice, IL-35 has been shown to be constitutively expressed by CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg cells) and suggested to contribute to their suppressive activity. In this study, we investigated whether human Treg cells express ILL-35. Double-staining analysis of human thymuses showed that neither Foxp3(+) nor CD25(+) cells coexpressed EB13. Similarly, Foxp3(+) cells present in human lymph nodes, tonsils, spleens, and intestines did not express EB13. Consistent with these in situ observations, Treg cells purified from blood or tonsils were negative for EB13 by immunoblotting. Other human T cell subsets, including effector T cells, naive and memory CD4(+) T cells, CD8(+) and gamma delta T cells also did not constitutively express EB13, which contrasts with IL-35 expression observed in murine CD8(+) and gamma delta T cells. Furthermore, although CD3/CD28 stimulation consistently induced low levels of EB13 in various CD4(+) T cell subsets, no EB13 could be detected in CD3/CD28-stimulated Treg cells. RT-PCR analysis showed that, whereas p35 transcripts were detected in both Teff and Treg cells, EB13 transcripts were detected only in activated Teff cells, but not in resting or activated Treg cells. Thus, in contrast to their murine counterpart, human Treg cells do not express detectable amounts of IL-35. The Journal of Immunology, 2008, 181: 6898-6905.