Chu R S, Askew D, Noss E H, Tobian A, Krieg A M, Harding C V
Department of Pathology, Division of Infectious Diseases, Case Western Reserve University, Cleveland, OH 44106, USA.
J Immunol. 1999 Aug 1;163(3):1188-94.
Unmethylated CpG motifs in bacterial DNA or short oligodeoxynucleotides (ODN) stimulate cells of the immune system and provide adjuvant activity. CpG DNA directly activates macrophages to secrete IL-12 and TNF-alpha and increases transcription of various genes, but its effects on macrophage Ag processing remain uncertain. The effects of CpG ODN on class II MHC (MHC-II) Ag processing and presentation were examined using peritoneal macrophages that were cultured for 18 h with CpG ODN and then pulsed with protein Ags. T cell hybridomas were used to detect presentation of specific peptide:MHC-II complexes. Both CpG ODN and LPS inhibited processing of bovine RNase and hen egg lysozyme. Presentation of exogenous peptides was inhibited to a lesser degree. Treatment of macrophages for 18 h with CpG ODN decreased surface MHC-II expression, as measured by flow cytometry. Furthermore, Northern blot analysis revealed that treatment with CpG ODN decreased I-Ak mRNA. Endocytosis by macrophages, as measured by uptake of fluorescent dextran, was not altered by treatment with CpG ODN. The inhibitory effect of CpG ODN on Ag processing was seen after prolonged (18 h) treatment of macrophages, but not after short treatment (e.g., 2 h) with CpG ODN and protein Ag. Enhancement of macrophage Ag processing was not seen at any time point of CpG ODN exposure, in contrast to data from other studies with dendritic cells. In summary, exposure of macrophages to CpG ODN results in a decrease in macrophage Ag processing and presentation, which is largely mediated by a decrease in synthesis of MHC-II molecules.
细菌DNA或短寡脱氧核苷酸（ODN）中的未甲基化CpG基序可刺激免疫系统细胞并具有佐剂活性。CpG DNA直接激活巨噬细胞分泌IL-12和TNF-α，并增加各种基因的转录，但其对巨噬细胞抗原加工的影响仍不确定。使用与CpG ODN培养18小时然后用蛋白抗原脉冲处理的腹膜巨噬细胞，研究了CpG ODN对II类主要组织相容性复合体（MHC-II）抗原加工和呈递的影响。T细胞杂交瘤用于检测特定肽：MHC-II复合物的呈递。CpG ODN和LPS均抑制牛核糖核酸酶和鸡蛋清溶菌酶的加工。外源性肽的呈递受到的抑制程度较小。通过流式细胞术测量，用CpG ODN处理巨噬细胞18小时可降低表面MHC-II表达。此外，Northern印迹分析显示，用CpG ODN处理可降低I-Ak mRNA水平。通过荧光葡聚糖摄取测量的巨噬细胞内吞作用，未因用CpG ODN处理而改变。在巨噬细胞经长时间（18小时）用CpG ODN处理后，可观察到CpG ODN对抗原加工的抑制作用，但在用CpG ODN和蛋白抗原进行短时间处理（例如2小时）后则未观察到。与来自其他树突状细胞研究的数据相反，在CpG ODN暴露的任何时间点均未观察到巨噬细胞抗原加工的增强。总之，巨噬细胞暴露于CpG ODN会导致巨噬细胞抗原加工和呈递减少，这在很大程度上是由MHC-II分子合成减少介导的。
