Wang Fengming, Chen Lei, Shen Qiong, Liu Tong, Jiang Lian, Gu Xinhua, Chen Lujun, Sun Jing, Liu Cuiping
Testing Center, Center for Disease Prevention and Control, Changzhou 213000, Jiangsu, China; Institute of Medical Biotechnology, Medical College of Soochow University, Suzhou 215007, Jiangsu, China.
Department of Endocrinology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, China.
Immunol Lett. 2015 May;165(1):47-51. doi: 10.1016/j.imlet.2015.03.010. Epub 2015 Mar 31.
During autoimmune disease the fraction of CD4+CD28- T cells in the peripheral blood of has been found to be elevated. In the present study, peripheral blood was collected from 61 patients with Graves' disease (GD) and 30 healthy control participants. Serum concentrations of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and thyrotropin receptor autoantibody (TRAb) were measured and peripheral blood mononuclear cell (PBMC) surface expression of CD4 and CD28 molecules was detected by flow cytometry. CD4+CD28- cells were sorted from six patients undergoing subtotal thyroidectomy and cultured ex vivo. The influence of TSH pretreated thyroid follicular cells on CD4+CD28- cell proliferation was evaluated using the agonist CD40 mAb 5C11, the blocking CD40L mAb 4F1 or B7-1 mAb 4E5 in 3H-TdR assays. Our data showed that the fraction of CD4+CD28- T cells was higher in GD patients than healthy donors (10.21%±8.56% vs. 2.33%±1.94%; P<0.001), and further elevated in 24 of 61 patients with Graves' ophthalmopathy (GO) (7.00±6.57% vs. 15.21±8.96%; P<0.001). A higher proportion of CD4+CD28- cells was detected in patients with degree II or III goiter than those with degree I goiter (11.53±9.18% vs. 6.11±3.97%; P<0.05 and 14.50±10.41% vs. 6.11±3.97%; P<0.01). The percentage of CD4+CD28- T cells correlated positively with serum levels of FT3 (r=0.354, P<0.01) and TRAb (r=0.304, P<0.05), but did not correlate with serum FT4 or TSH. Ex vivo, 5C11 enhanced proliferation of CD4+CD28+ cells (P<0.05), but did not influence the proliferation of CD4+CD28- cells. 4F1 inhibited the proliferation of both CD4+CD28+ (P<0.05) and CD4+CD28- (P<0.01) cells, and 4E5 inhibited proliferation of CD4+CD28+ cells (P<0.05). The elevation in circulating CD4+CD28- cells in GD patients correlates with disease severity and maybe plays an important role in the pathogenesis of GD.
在自身免疫性疾病期间，已发现外周血中CD4 + CD28 - T细胞的比例升高。在本研究中，采集了61例格雷夫斯病（GD）患者和30名健康对照者的外周血。检测血清促甲状腺激素（TSH）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）和促甲状腺素受体自身抗体（TRAb）的浓度，并通过流式细胞术检测外周血单个核细胞（PBMC）表面CD4和CD28分子的表达。从6例接受甲状腺次全切除术的患者中分离出CD4 + CD28 - 细胞，并进行体外培养。在3H - TdR试验中，使用激动剂CD40单克隆抗体5C11、阻断性CD40L单克隆抗体4F1或B7 - 1单克隆抗体4E5评估经TSH预处理的甲状腺滤泡细胞对CD4 + CD28 - 细胞增殖的影响。我们的数据显示，GD患者外周血中CD4 + CD28 - T细胞的比例高于健康供者（10.21%±8.56%对2.33%±1.94%；P < 0.001），并且在61例格雷夫斯眼病（GO）患者中的24例中进一步升高（7.00±6.57%对15.21±8.96%；P < 0.001）。与I度甲状腺肿患者相比，II度或III度甲状腺肿患者中检测到更高比例的CD4 + CD28 - 细胞（11.53±9.18%对6.11±3.97%；P < 0.05和14.50±10.41%对6.11±3.97%；P < 0.01）。CD4 + CD28 - T细胞的百分比与血清FT3水平（r = 0.354，P < 0.01）和TRAb水平（r = 0.304，P < 0.05）呈正相关，但与血清FT4或TSH无关。在体外，5C11增强了CD4 + CD28 + 细胞的增殖（P < 0.05），但不影响CD4 + CD28 - 细胞的增殖。4F1抑制了CD4 + CD28 + 细胞（P < 0.05）和CD4 + CD28 - 细胞（P < 0.01）的增殖，4E5抑制了CD4 + CD28 + 细胞的增殖（P < 0.05）。GD患者循环中CD4 + CD28 - 细胞的升高与疾病严重程度相关，可能在GD的发病机制中起重要作用。
