Effects of dendritic cells modified with transforming growth factor ?1 gene on the attack of myasthenia gravis in rats / 中华神经科杂志

ABSTRACT

Objective To study the effects of dendritic cells (DC) modified with transforming growth factor ?1 (TGF-?1) gene on experimental autoimmune myasthenia gravis (EAMG) in Lewis rats. Methods 30 female Lewis rats were divided randomly into 6 groups normal group, EAMG group, DCs treatment group, pcDNA_3-TGF-?1-DCs treatment group, pcDNA_3-DCs treatment group and normal saline group. The rats were immunized with the acetylcholine receptor (AChR) protein extracted from electric organ of Narcine timilei and completed Freund’s adjuvant (CFA) in the experiment groups except normal group. 2?106 pcDNA_3-TGF-?1-DCs/rat were injected subcutaneously into the backs of the rats that had been immunized 5 days earlier with AChR+CFA. The rats in DCs treatment group, pcDNA_3-DCs treatment group and normal saline group were injected in parallel with untreated DCs, pcDNA_3-DCs and normal saline respectively. Then the clinical manifestations were observed everyday. And 7 weeks after the first immunization, repetitive nerve stimulation, detection of acetylcholine receptor antibody (AChRab) and ultrastructural study of neuromuscular junction (NMJ) were performed. Results (1) The mild symptoms were observed on 1 or 2 rats in the experiment groups except normal group after a week, which lasted for 2 to 5 days. After about 5 weeks, the rats in EAMG group, DCs treatment group, pcDNA_3-DCs treatment group and normal saline group presented some symptoms at different degree like myasthenia gravis, and only one of the rats in pcDNA_3-TGF-?1-DCs treatment group presented mildly decreased activity. (2) The significant decrement of repetitive nerve stimulation were found in EAMG group, DCs treatment group, pcDNA_3-DCs treatment group and normal saline group(16.75?6.13, 17.75?7.81, 18.25?8.22 and 16.50?7.14, respectively), but there was no attenuation in pcDNA_3-TGF-?1-DCs treatment group and normal group(3.20?3.70 and 5.60?2.70, respectively). The percentage of decrement in pcDNA_3-TGF-?1-DCs treatment group was lower than that in EAMG group(5.60?2.70 and 16.75?6.13, respectively,P0.05). (4) The combined AChRs in NMJ of the rats in pcDNA_3-TGF-?1-DCs group were higher than that in EAMG group, and the structure changes of the synapse were relieved.Conclusion It suggests that DCs, transfected with pcDNA_3-TGF-?1, when injected subcutaneously into Lewis rats with incipient EAMG, could inhibit the production of AChR-Ab, relieve the pathologic changes in NMJ and ameliorate the development of EAMG.