Elevated double negative T cells in pediatric autoimmunity.

Elevated double negative T cells in pediatric autoimmunity.
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DOI:
10.1007/s10875-014-0038-z
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发表时间:
2014-07
影响因子:
9.1
通讯作者:
Cooper MA
Cooper MA
中科院分区:
医学2区
文献类型:
--
作者:
Tarbox JA;Keppel MP;Topcagic N;Mackin C;Ben Abdallah M;Baszis KW;White AJ;French AR;Cooper MA

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自身免疫性疾病被认为是由免疫系统自身耐受性的丧失引起的。自身免疫性疾病中免疫失调的一个候选标志物是外周中存在增加的双阴性T细胞(DNT)。DNT在自身免疫性淋巴组织增生综合征中特征性升高,这是一种由Fas通路缺陷引起的淋巴细胞凋亡缺陷引起的全身性自身免疫性疾病。DNT还在系统性红斑狼疮(SLE)成人患者的外周血中发现,它们可能是致病的。DNT在儿童自身免疫性疾病尚未调查。我们评估了DNT在SLE、混合性结缔组织病(MCTD)、幼年特发性关节炎(JIA)或抗核抗体(ANA)升高但无全身性疾病的儿科患者中的应用。通过流式细胞术分析了54名儿科患者外周血单核细胞的DNT(CD 3 + CD 56-TCRαβ+ CD 4-CD 8-),其中包括:23名SLE、15名JIA、11名ANA和5名MCTD,并与28名健康对照进行了比较。与1例(3.6%)对照组相比,16例(29.6%)DNT升高(≥ 2.5%的CD 3 + CD 56 −TCRαβ+细胞)。包括细胞毒性药物和绝对淋巴细胞计数在内的药物使用与DNT水平无关,DNT的百分比随时间推移而稳定。多种表型和活化标记物的分析显示,与对照组相比,自身免疫性疾病患者DNT上的CD 45 RA表达增加。DNT在患有自身免疫性疾病的儿科患者中升高,需要进行额外的研究以确定其在自身免疫中的确切作用。
Autoimmune diseases are thought to be caused by a loss of self-tolerance of the immune system. One candidate marker of immune dysregulation in autoimmune disease is the presence of increased double negative T cells (DNTs) in the periphery. DNTs are characteristically elevated in autoimmune lymphoproliferative syndrome, a systemic autoimmune disease caused by defective lymphocyte apoptosis due to Fas pathway defects. DNTs have also been found in the peripheral blood of adult patients with systemic lupus erythematosus (SLE), where they may be pathogenic. DNTs in children with autoimmune disease have not been investigated. We evaluated DNTs in pediatric patients with SLE, mixed connective tissue disease (MCTD), juvenile idiopathic arthritis (JIA), or elevated antinuclear antibody (ANA) but no systemic disease. DNTs (CD3+CD56−TCRαβ+CD4−CD8−) from peripheral blood mononuclear cells were analyzed by flow cytometry from 54 pediatric patients including: 23 SLE, 15 JIA, 11 ANA and 5 MCTD compared to 28 healthy controls. Sixteen cases (29.6%) had elevated DNTs (≥ 2.5% of CD3+CD56−TCRαβ+ cells) compared to 1 (3.6%) control. Medication usage including cytotoxic drugs and absolute lymphocyte count were not associated with DNT levels, and percentages of DNTs were stable over time. Analysis of multiple phenotypic and activation markers showed increased CD45RA expression on DNTs from patients with autoimmune disease compared to controls. DNTs are elevated in a subset of pediatric patients with autoimmune disease and additional investigations are required to determine their precise role in autoimmunity.
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