Jonson C-O, Pihl M, Nyholm C, Cilio C M, Ludvigsson J, Faresjö M
Division of Pediatrics and Diabetes Research Centre, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Clin Exp Immunol. 2008 Aug;153(2):174-81. doi: 10.1111/j.1365-2249.2008.03625.x. Epub 2008 Jun 28.
Extracorporeal photochemotherapy (ECP) has demonstrated immunological effects. The proposed cytotoxic lymphocyte antigen 4 (CTLA-4) involvement, together with forkhead box P3 (FoxP3) and transforming growth factor (TGF)-beta are associated with regulatory T cell activity. The aim of the study was to evaluate the regulatory T cell-associated effect of ECP in recent onset type 1 diabetic (T1D) children. Children (n = 20) with T1D received photopheresis 8-methoxypsoralen + ECP or placebo + shampheresis. Peripheral blood mononuclear cells (PBMC) collected pretreatment (day 1) and post-treatment (day 90) were stimulated with phytohaemagglutinin (PHA) and T1D-associated glutamic acid decarboxylase 65 (GAD(65)) peptide a.a. 247-279. CTLA-4, sCTLA-4, FoxP3 and TGF-beta mRNA transcription was quantified. Photopheresis-treated individuals' relative mRNA expression was generally maintained during the course of the study. Placebo individuals increased in spontaneous CTLA-4 mRNA (P < 0.05) but decreased in expression after stimulation with GAD(65)-peptide (P < 0.05) and PHA (P < 0.05). Spontaneous TGF-beta (P < 0.05) increased whereas PHA- (P < 0.01) and GAD(65)-peptide (P < 0.01)-induced TGF-beta expression decreased in the placebo group, whereas it was maintained in the treated group. Without intervention, expression of CTLA-4 and TGF-beta, stimulated with PHA and GAD(65) peptide, decreased with time, with a parallel reduction of GAD(65)-peptide and PHA-stimulated TGF-beta expression. These parameters were counteracted by ECP. In conclusion, our results indicate that ECP maintains regulatory T cell-associated activity in recent-onset T1D.
体外光化学疗法（ECP）已显示出免疫效应。所提出的细胞毒性淋巴细胞抗原4（CTLA-4）的参与，以及叉头框P3（FoxP3）和转化生长因子（TGF）-β与调节性T细胞活性相关。本研究的目的是评估ECP对近期发病的1型糖尿病（T1D）儿童调节性T细胞相关的影响。患有T1D的儿童（n = 20）接受光分离置换疗法8-甲氧基补骨脂素+ ECP或安慰剂+假光分离置换疗法。收集治疗前（第1天）和治疗后（第90天）的外周血单个核细胞（PBMC），用植物血凝素（PHA）和T1D相关的谷氨酸脱羧酶65（GAD(65)）肽a.a. 247-279进行刺激。对CTLA-4、sCTLA-4、FoxP3和TGF-β mRNA转录进行定量。在研究过程中，接受光分离置换疗法治疗个体的相对mRNA表达总体保持稳定。接受安慰剂治疗的个体自发CTLA-4 mRNA增加（P < 0.05），但在用GAD(65)肽（P < 0.05）和PHA（P < 0.05）刺激后表达下降。安慰剂组中自发TGF-β（P < 0.05）增加，而PHA（P < 0.01）和GAD(65)肽（P < 0.01）诱导的TGF-β表达下降，而在治疗组中保持稳定。在没有干预的情况下，PHA和GAD(65)肽刺激的CTLA-4和TGF-β表达随时间下降，同时GAD(65)肽和PHA刺激的TGF-β表达也平行降低。这些参数被ECP抵消。总之，我们的结果表明ECP可维持近期发病的T1D中调节性T细胞相关活性。
