Dudina M A, Savchenko A A, Dogadin S A, Borisov A G, Belenyuk V D
Krasnoyarsk State Medical University; Krasnoyarsk regional clinical hospital.
Krasnoyarsk State Medical University; Federal Research Center «Krasnoyarsk Science Center».
Probl Endokrinol (Mosk). 2023 Jun 30;69(3):35-43. doi: 10.14341/probl13223.
The content of regulatory T cells (Treg) at different stages in formation of effector subpopulations and the level of CD25 expression on the membrane of their various fractions in Graves' disease can determine the long-term autoimmune process persistence and be the target of immunotropic therapy of the disease.
To study the features of regulatory T-blood cells subpopulation and the level of CD25 expression in patients with Graves' disease in dynamics after radioactive iodine therapy (RIT) to identify the specific Treg subpopulations for potential immunotropic therapy targets of the disease.
A single-center, prospective, cohort, open, controlled study was conducted with the participation of women with laboratory-confirmed Graves' disease. The features of regulatory T-blood cells subpopulation and the level of expression (MFI) CD25 surface receptor were studied by flow cytometry using direct immunofluorescence using monoclonal antibodies.
The study included 36 women with recurrent Graves' disease, middle age 46.34±14.32 years. In patients with Graves' disease before and during the entire period after RIT a low percentage of naive (CD45R0-CD62L+) and terminally differentiated (CD45R0-CD62L-) Treg was established relative to the control, and on 3 and 6 months after RIT a significant decrease of cells with this phenotype was revealed relative to the values detected in patients before and 1 month after RIT (p<0.001). Against the background of compensated hypothyroidism the most significant changes of expression CD25 receptor in patients with Graves' disease were found on 3 and 6 months after RIT: reduced levels of MFI CD25 on surface of naive and terminally differentiated Treg.
A decrease in the level of naive Treg was found (apparently due to a violation of differentiation processes in thymus) and terminally differentiated Tregs (due to maturation and survival processes), which are supplemented by a reduced expression of the CD25 receptor on the surface of these cells and do not depend on hyperthyroidism compensation, the titer of TSH receptor antibodies, previous conservative therapy with thiamazole and RIT. The obtained new data reveal the role of naive and terminally differentiated Treg subpopulations in immunopathogenesis and help to outline further ways to develop approaches for immunotropic therapy.
在格雷夫斯病效应子亚群形成的不同阶段，调节性T细胞（Treg）的含量及其不同组分细胞膜上CD25的表达水平可决定自身免疫过程的长期持续存在，并成为该疾病免疫调节治疗的靶点。
研究放射性碘治疗（RIT）后动态变化过程中格雷夫斯病患者调节性T淋巴细胞亚群的特征及CD25的表达水平，以确定特定的Treg亚群作为该疾病潜在的免疫调节治疗靶点。
开展一项单中心、前瞻性、队列、开放、对照研究，纳入实验室确诊为格雷夫斯病的女性患者。采用直接免疫荧光法，利用单克隆抗体通过流式细胞术研究调节性T淋巴细胞亚群的特征及CD25表面受体的表达水平（平均荧光强度）。
该研究纳入了36例复发性格雷夫斯病女性患者，平均年龄为46.34±14.32岁。与对照组相比，格雷夫斯病患者在RIT前及整个RIT后期间，幼稚（CD45R0-CD62L+）和终末分化（CD45R0-CD62L-）Treg的比例较低，且与RIT前及RIT后1个月检测到的值相比，RIT后3个月和6个月时具有这种表型的细胞显著减少（p<0.001）。在甲状腺功能减退得到代偿的背景下，格雷夫斯病患者在RIT后3个月和6个月时CD25受体表达的变化最为显著：幼稚和终末分化Treg表面的CD25平均荧光强度水平降低。
发现幼稚Treg水平降低（显然是由于胸腺中分化过程受到破坏）以及终末分化Treg水平降低（由于成熟和存活过程），这些细胞表面的CD25受体表达也降低，且这与甲状腺功能亢进的代偿、促甲状腺激素受体抗体滴度、先前使用甲巯咪唑的保守治疗及RIT无关。获得的新数据揭示了幼稚和终末分化Treg亚群在免疫发病机制中的作用，并有助于勾勒出进一步开发免疫调节治疗方法的途径。
