CD62L(neg)CD38⁺ expression on circulating CD4⁺ T cells identifies mucosally differentiated cells in protein fed mice and in human celiac disease patients and controls.
CD62L(neg)CD38⁺ expression on circulating CD4⁺ T cells identifies mucosally differentiated cells in protein fed mice and in human celiac disease patients and controls.
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DOI：
10.1038/ajg.2011.24
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发表时间：
2011-06
影响因子：
9.8
通讯作者：
Samsom, Janneke N.
中科院分区：
文献类型：
--
作者：
du Pre, M. Fleur;van Berkel, Lisette A.;Raki, Melinda;van Leeuwen, Marieke A.;de Ruiter, Lilian F.;Broere, Femke;ter Borg, Mariette N. D.;Lund, Frances E.;Escher, Johanna C.;Lundin, Knut E. A.;Sollid, Ludvig M.;Kraal, Georg;Nieuwenhuis, Edward E. S.;Samsom, Janneke N.
本研究的目的是确定粘膜T细胞的新标记物，以监测外周血中正在进行的肠道免疫反应。在小鼠中研究了在卵清蛋白（OVA）喂养后肠引流肠系膜淋巴结（MLN）中卵清蛋白（OVA）特异性T细胞上细胞表面标志物的表达。局部粘膜介质视黄酸（RA）和TGF-β对粘膜表型诱导的影响在体外T细胞分化试验中用鼠和人T细胞测定。进行四聚体染色以研究患有乳糜泻（一种慢性小肠炎症）的患者循环中的谷蛋白特异性T细胞。在小鼠中，在耐受诱导和肠道内稳态消除期间，MLN中增殖的T细胞均为CD 62 L + CD 38+。在小鼠中，这种粘膜CD 62 L + CD 38 + T细胞表型被RA和TGF-β有效地诱导，而对于人CD 4 + T细胞，单独的RA就足够了。CD 4 + CD 62 + CD 38 + T细胞表型可用于鉴定人外周血中粘膜来源的T细胞，因为肠道归巢趋化因子受体CCR 9和β7整联蛋白在该亚群中高度富集，而皮肤白细胞相关抗原的表达几乎不存在。四聚体染色显示，谷蛋白特异性T细胞出现在血液中的治疗乳糜泻患者口服谷蛋白的挑战后，主要是CD 4 + CD 62 LCD 38+。CD 4 T细胞的循环CD 62 + CD 38+的总百分比不是肠道炎症的指标，因为儿科乳糜泻患者、炎性肠病患者和相应对照之间的百分比没有差异。然而，粘膜T细胞的表型选择允许细胞因子谱分析，因为在再刺激CD 62 L后，在循环粘膜T细胞中容易检测到CD 38+细胞IL-10和IFN-γ转录物。通过选择占总CD 4 + T细胞库中5-10%细胞的CD 62 + CD 38+表达，我们能够高度富集对粘膜抗原具有特异性的效应T细胞。这对于功能研究至关重要，因为这种纯化增强了细胞因子检测和细胞活化的灵敏度。
The aim of this study was to identify new markers of mucosal T cells to monitor ongoing intestinal immune responses in peripheral blood. Expression of cell-surface markers was studied in mice on ovalbumin (OVA)-specific T cells in the gut-draining mesenteric lymph nodes (MLN) after OVA feed. The effect of the local mucosal mediators retinoic acid (RA) and TGF-β on the induction of a mucosal phenotype was determined in in vitro T-cell differentiation assays with murine and human T cells. Tetramer stainings were performed to study gluten-specific T cells in the circulation of patients with celiac disease, a chronic small intestinal inflammation. In mice, proliferating T cells in MLN were CD62LnegCD38+ during both tolerance induction and abrogation of intestinal homeostasis. This mucosal CD62LnegCD38+ T-cell phenotype was efficiently induced by RA and TGF-β in mice, whereas for human CD4+ T cells RA alone was sufficient. The CD4+CD62LnegCD38+ T-cell phenotype could be used to identify T cells with mucosal origin in human peripheral blood, as expression of the gut-homing chemokine receptor CCR9 and β7 integrin were highly enriched in this subset whereas expression of cutaneous leukocyte associated antigen was almost absent. Tetramer staining revealed that gluten-specific T cells appearing in blood of treated celiac disease patients after oral gluten challenge were predominantly CD4+CD62LnegCD38+. The total percentage of circulating CD62LnegCD38+ of CD4 T cells was not an indicator of intestinal inflammation as percentages did not differ between pediatric celiac disease patients, inflammatory bowel disease patients and respective controls. However, the phenotypic selection of mucosal T cells allowed cytokine profiling as upon restimulation of CD62LnegCD38+ cells IL-10 and IFN-γ transcripts were readily detected in circulating mucosal T-cells. By selecting for CD62LnegCD38+ expression which comprises 5–10% of the cells within the total CD4+ T-cell pool we are able to highly enrich for effector T cells with specificity for mucosal antigens. This is of pivotal importance for functional studies as this purification enhances the sensitivity of cytokine detection and cellular activation.
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DOI：
10.1084/jem.178.1.187
发表时间：
1993-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lundin KE;Scott H;Hansen T;Paulsen G;Halstensen TS;Fausa O;Thorsby E;Sollid LM
通讯作者：
Sollid LM
DOI：
10.1073/pnas.0505018102
发表时间：
2005-10-04
影响因子：
11.1
作者：
Chen, QY;Ross, AC
通讯作者：
Ross, AC
GATA3驱动的Th2响应抑制TGF-BETA1诱导的FOXP3表达和调节T细胞的形成。
影响因子：
9.8
作者：
Mantel PY;Kuipers H;Boyman O;Rhyner C;Ouaked N;Rückert B;Karagiannidis C;Lambrecht BN;Hendriks RW;Crameri R;Akdis CA;Blaser K;Schmidt-Weber CB
通讯作者：
Schmidt-Weber CB
影响因子：
8
作者：
Broere, F.;du Pre, M. F.;Samsom, J. N.
通讯作者：
Samsom, J. N.
影响因子：
32.4
作者：
Partida-Sánchez, S;Goodrich, S;Lund, FE
通讯作者：
Lund, FE