使用针对T细胞相关分子的单克隆抗体,通过细胞计数法确定健康成年人中CD4及CD4CD25Foxp3CD127调节性T细胞群体的频率和稳定性。
Frequency and stability of populations of CD4 and CD4CD25Foxp3CD127 Treg in healthy adults defined by cytometry using monoclonal antibodies to T cell associated molecules.
作者信息
Verma Nirupama D, Al-Atiyah Ranje, Rakesh Prateek, Lam Andrew D, Chiu Christopher, Tran Giang T, Hall Bruce M, Hodgkinson Suzanne J
机构信息
Immune Tolerance Laboratory, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia.
School of Clinical Medicine, Southwest Sydney Campus, Faculty of Medicine and Health, UNSW Australia, Liverpool, New South Wales, Australia.
出版信息
Cytometry B Clin Cytom. 2025 Jul;108(4):282-298. doi: 10.1002/cyto.b.22241. Epub 2025 Jun 4.
Monitoring subpopulations of CD4 T cells in blood, especially regulatory CD4CD25Foxp3CD127T cells, has the potential to identify tolerance to transplants and defects that cause autoimmunity. CD45RA is expressed by naïve/resting CD4, not by activated cells. Staining CD45RA with CD25 or Foxp3 identifies five populations of CD4 T cells, three Treg, and two CD4Foxp3T cells. CD25 is induced on activation of effector cells and is constitutively expressed by Treg. Examining Foxp3 cells in CD4CD25CD127, identified three Treg populations. It is not known how stable these populations of CD4T cells are within individuals and between individuals. Repeated estimations over 3 years in 10 HV showed the proportion of cells in the three Treg populations was stable, whereas the two Foxp3 populations varied. In a larger cohort of 110 samples, females had higher numbers of CD4 cells than males. As a percentage of lymphocytes, there was no sex difference in the proportion of cells in the five populations. With age, there were fewer total Treg, with fewer resting Treg but an increase in activated Treg. Activation of both naïve CD4 T cells and Treg induces expression of chemokine receptors associated with Th1, Th17, and Th2 responses that promote their infiltration into sites of inflammation. Activated Treg expressed CCR4 and, in addition, expressed CXCR3 (Th1), CCR6 (Th17), or neither CXCR3 nor CCR6 (Th2). Some Treg expressed both CCR6 and CXCR3. HLA-DR and CD39 were expressed by activated Treg, and many cells expressed both. There was low PD-1 expression. The stability of the major Treg populations suggested it could be feasible to establish normal ranges for the three Treg populations. Staining for chemokine receptors and Treg effector molecules in activated Treg populations may detect changes in immune homeostasis and tolerance.
监测血液中CD4 T细胞亚群,尤其是调节性CD4CD25Foxp3CD127T细胞,有可能识别对移植的耐受性以及导致自身免疫的缺陷。CD45RA由初始/静息CD4表达,而非活化细胞表达。用CD25或Foxp3对CD45RA进行染色可识别出五种CD4 T细胞群体,三种调节性T细胞(Treg)和两种CD4Foxp3T细胞。CD25在效应细胞激活时被诱导表达,并由Treg组成性表达。检测CD4CD25CD127中的Foxp3细胞,可识别出三种Treg群体。目前尚不清楚这些CD4T细胞群体在个体内部和个体之间的稳定性如何。对10名健康志愿者(HV)进行的为期3年的重复评估显示,三种Treg群体中的细胞比例是稳定的,而两种Foxp3群体则有所变化。在一个包含110个样本的更大队列中,女性的CD4细胞数量高于男性。作为淋巴细胞的百分比,五种群体中细胞的比例没有性别差异。随着年龄增长,总的Treg数量减少,静息Treg数量减少,但活化Treg数量增加。初始CD4 T细胞和Treg的激活均会诱导与Th1、Th17和Th2反应相关的趋化因子受体表达,从而促进它们浸润到炎症部位。活化的Treg表达CCR4,此外,还表达CXCR3(Th1)、CCR6(Th17),或者既不表达CXCR3也不表达CCR6(Th2)。一些Treg同时表达CCR6和CXCR3。活化的Treg表达HLA-DR和CD39,许多细胞同时表达这两种分子。PD-1表达水平较低。主要Treg群体的稳定性表明,为三种Treg群体建立正常范围可能是可行的。对活化Treg群体中的趋化因子受体和Treg效应分子进行染色,可能会检测到免疫稳态和耐受性的变化。