Pendeloski Karen Priscilla Tezotto, Mattar Rosiane, Torloni Maria Regina, Gomes Caio Perez, Alexandre Sandra Maria, Daher Silvia
Department of Obstetrics, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, 9 Andar, São Paulo, SP, 04939 032, Brazil.
Endocrine. 2015 Sep;50(1):99-109. doi: 10.1007/s12020-015-0567-0. Epub 2015 Mar 10.
Induction of maternal-fetal immune tolerance is essential for the development of normal pregnancy. Impaired expression of costimulatory molecules may lead to intense inflammatory reaction, a mechanism involved in the pathophysiology of gestational diabetes mellitus (GDM). The aim of this study was to investigate whether immunoregulatory molecules are involved in the physiopathology of GDM. This case-control study included 30 healthy pregnant women and 20 GDM patients. Flow cytometry was used to assess peripheral blood T subpopulations (CD4(+) and CD8(+)), the expression of immunoregulatory molecules (CD28, ICOS, CTLA-4, and PD-1) and activation markers (CD69 and HLA-DR). Compared to healthy women, GDM patients had a significantly higher frequency of CD4(+)CD69(+) and CD8(+)CD69(+) T cells; only patients with insulin-treated GDM had increased numbers of CD4(+)HLA-DR(+) T cells. We also observed significantly higher percentages of CD4(+)CD28(+)HLA-DR(+), CD3(+)CD4(+)ICOS(+), CD3(+)CD4(+)PD-1(+), CD8(+)CD28(+)CD69(+), CD8(+)CD28(+)HLA-DR(+), CD8(+)CTLA-4(+)HLA-DR(+), and CD3(+)CD8(+)ICOS(+) T cells and lower frequency of CD3(+)CD4(+)CTLA-4(+), CD3(+)CD8(+)CTLA-4(+), and CD8(+)ICOS(+)HLA-DR(+) T cells in GDM patients compared to healthy pregnant women. This first study assessing costimulatory molecules in GDM patients shows that these patients have exacerbated markers of T cell activation along with CTLA-4 deficiency, findings that indicate that the maternal-fetal tolerance is compromised in these patients.
诱导母胎免疫耐受对正常妊娠的发展至关重要。共刺激分子表达受损可能导致强烈的炎症反应，这是妊娠期糖尿病（GDM）病理生理学中的一种机制。本研究的目的是调查免疫调节分子是否参与GDM的病理生理过程。这项病例对照研究纳入了30名健康孕妇和20名GDM患者。采用流式细胞术评估外周血T亚群（CD4(+)和CD8(+)）、免疫调节分子（CD28、ICOS、CTLA - 4和PD - 1）的表达以及活化标志物（CD69和HLA - DR）。与健康女性相比，GDM患者中CD4(+)CD69(+)和CD8(+)CD69(+) T细胞的频率显著更高；仅接受胰岛素治疗的GDM患者中CD4(+)HLA - DR(+) T细胞数量增加。我们还观察到，与健康孕妇相比，GDM患者中CD4(+)CD28(+)HLA - DR(+)、CD3(+)CD4(+)ICOS(+)、CD3(+)CD4(+)PD - 1(+)、CD8(+)CD28(+)CD69(+)、CD8(+)CD28(+)HLA - DR(+)、CD8(+)CTLA - 4(+)HLA - DR(+)和CD3(+)CD8(+)ICOS(+) T细胞的百分比显著更高，而CD3(+)CD4(+)CTLA - 4(+)、CD3(+)CD8(+)CTLA - 4(+)和CD8(+)ICOS(+)HLA - DR(+) T细胞的频率更低。这项首次评估GDM患者共刺激分子的研究表明，这些患者具有加剧的T细胞活化标志物以及CTLA - 4缺陷，这些发现表明这些患者的母胎耐受性受损。
