Vuckovic Slavica, Withers Geoff, Harris Mark, Khalil Dalia, Gardiner Damien, Flesch Inge, Tepes Sonia, Greer Ristan, Cowley David, Cotterill Andrew, Hart Derek N J
Mater Medical Research Institute, Aubigny Place, Raymond Tce, South Brisbane, QLD 4101, Australia.
Clin Immunol. 2007 Jun;123(3):281-8. doi: 10.1016/j.clim.2007.03.002. Epub 2007 Apr 25.
In this study DC numbers, phenotype and DC responses to the Toll-like receptor (TLR)-3 ligand, poly I:C, were examined in new-onset Type 1 diabetes (T1D) patients (ND) and in established T1D patients (ED). Absolute blood myeloid DC (MDC) and plasmacytoid DC (PDC) numbers were decreased in ND and ED patients compared to age-matched controls. The decrease in MDC and PDC counts was less evident in patients with a combination of T1D and coeliac disease (CD) or CD alone. The age-dependent decline in blood DC numbers, found in control children, was not evident in ND patients, such that 2-10 years old ND children had similar MDC and PDC numbers to 15-17 years old controls. In ED patients the t-score of MDC and PDC numbers related to the age of diagnosis but not to disease duration. Blood DC in T1D patients were not distinguished from those of controls by the levels of HLA-DR, CD40 and CD86 expression or the percentage of DC expressing cytokines, IL-12, IL-10, IL-6 and TNF-alpha, in responses to poly I:C. If low DC numbers are shown to contribute to the autoimmunity in T1D, interventions aimed to increase DC numbers may mitigate against beta-cell loss.
在本研究中,对新发1型糖尿病(T1D)患者(ND)和病程较长的T1D患者(ED)的树突状细胞(DC)数量、表型以及DC对Toll样受体(TLR)-3配体聚肌苷酸胞苷酸(poly I:C)的反应进行了检测。与年龄匹配的对照组相比,ND和ED患者的外周血髓样DC(MDC)和浆细胞样DC(pDC)的绝对数量均减少。在合并乳糜泻(CD)或仅患CD的T1D患者中,MDC和pDC数量的减少不太明显。在对照儿童中发现的血液DC数量随年龄的下降在ND患者中并不明显,因此2至10岁的ND儿童的MDC和pDC数量与15至17岁的对照儿童相似。在ED患者中,MDC和pDC数量的t值与诊断年龄相关,而与病程无关。T1D患者血液中的DC在HLA-DR、CD40和CD86的表达水平或对poly I:C反应中表达细胞因子白细胞介素(IL)-12、IL-10、IL-6和肿瘤坏死因子(TNF)-α的DC百分比方面与对照组没有区别。如果低DC数量被证明与T1D中的自身免疫有关,那么旨在增加DC数量的干预措施可能会减轻β细胞的损失。