Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
PLoS One. 2012;7(1):e29355. doi: 10.1371/journal.pone.0029355. Epub 2012 Jan 17.
Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these "excessive" responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself.
Cord blood (>37 week of gestation) and peripheral blood (healthy controls) were obtained and different Treg cell subsets were isolated. The suppressive potential of Treg populations after antigen exposure was evaluated via functional inhibition assays ([(3)H]thymidine incorporation assay and CFSE staining) with or without allergen stimulation. The frequency and markers of CD4(+)CD25(high)FoxP3(+) T cells were characterized by mRNA analysis and flow cytometry.
Cord blood derived CD4(+)CD25(high) cells did not show substantial suppressor capacity upon TCR activation, in contrast to CD4(+)CD25(high) cells freshly purified from adult blood. This could not be explained by a lower frequency of FoxP3(+)CD4(+)CD25(high)cells or FOXP3 mRNA expression. However, after antigen-specific stimulation in vitro, these cells showed strong proliferation and expansion and gained potent suppressive properties. The efficiency of their suppressive capacity can be enhanced in the presence of endotoxins. If T-cells were sorted according to their CD127 expression, a tiny subset of Treg cells (CD4(+)CD25(+)CD127(low)) is highly suppressive even without prior antigen exposure.
Cord blood harbors a very small subset of CD4(+)CD25(high) Treg cells that requires antigen-stimulation to show expansion and become functional suppressive Tregs.
在抗原暴露后，脐带血来源的 T 细胞通过高增殖对普遍存在的环境抗原产生反应。迄今为止，尚不清楚这些“过度”反应是否与假定的调节性 T 细胞 (Treg) 区室的不同调节特性有关，甚至与 Treg 区室本身的扩增有关。
获得脐带血（>37 周妊娠）和外周血（健康对照），并分离不同的 Treg 细胞亚群。通过功能抑制测定（[（3）H]胸苷掺入测定和 CFSE 染色）评估抗原暴露后 Treg 群体的抑制潜力，有或没有过敏原刺激。通过 mRNA 分析和流式细胞术来表征 CD4+CD25+FoxP3+T 细胞的频率和标记物。
与从成人血液中新鲜纯化的 CD4+CD25+细胞相比，脐带血来源的 CD4+CD25+细胞在 TCR 激活后没有表现出实质性的抑制能力。这不能用 FoxP3+CD4+CD25+细胞的频率或 FOXP3 mRNA 表达较低来解释。然而，在体外进行抗原特异性刺激后，这些细胞表现出强烈的增殖和扩增，并获得了有效的抑制特性。在存在内毒素的情况下，可以增强其抑制能力的效率。如果根据其 CD127 表达对 T 细胞进行分选，则一小部分 Treg 细胞（CD4+CD25+CD127(low)）即使在没有预先暴露抗原的情况下也具有高度抑制作用。
脐带血中存在一小部分 CD4+CD25+Treg 细胞，需要抗原刺激才能显示扩增并成为功能性抑制性 Treg 细胞。
