Wang Rong, Yang Huan, Xiao Bo, Zhang Li-Fang
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2009 Sep;40(5):793-7.
To explore the therapeutic effect of Talpha146-162-iMDCs on C57BL/6 mice with EAMG and the role of changes in B cell activation regulated by Cbl.
Thirty four adult male C57BL/6 mice were randomly divided into EAMG group (A group), EAMG group with interventions (B group) and control group (C group). T-AChR antigens were injected to the mice in A and B groups to induce EAMG. Meanwhile, dendritic cells from immature bone marrows were cultured and pulsed with Talpha146-162, and injected to the mice in the intervention group. The mRNA expression of Cbl was detected by RT-PCR 90 days after the termination of experiment. The expression and phosphorylation of Syk and Lyn proteins were measured by Western blot.
More mice (9/12, 75%) in A group developed EAMG than in B group (3/12, 25%, P<0.05). Mice in A group also suffered more serious illness in terms of clinical scores than mice in B group (1.69+/-1.12 vs 0.35+/-0.67, P<0.01). No EAMG occurred in mice in C group. Mice in B group had lower mRNA expressions of Cbl in the spleens and lymphonodes than mice in A groups, but both had higher expressions than mice in C group (P<0.05). Mice in B group had higher mRNA expression of Cbl than mice in A group (P<0.05).
Talpha146-162-iMDCs prevent EAMG, possibly through negative regulation of Cbl on BCR signaling.
探讨Tα146 - 162 - iMDCs对实验性自身免疫性重症肌无力(EAMG)C57BL/6小鼠的治疗作用以及Cbl调控的B细胞活化变化的作用。
34只成年雄性C57BL/6小鼠随机分为EAMG组(A组)、干预EAMG组(B组)和对照组(C组)。对A组和B组小鼠注射T - AChR抗原诱导EAMG。同时,培养来自未成熟骨髓的树突状细胞并用Tα146 - 162脉冲处理,然后注射到干预组小鼠体内。实验结束90天后,通过RT - PCR检测Cbl的mRNA表达。通过蛋白质免疫印迹法检测Syk和Lyn蛋白的表达及磷酸化情况。
A组发生EAMG的小鼠(9/12,75%)多于B组(3/12,25%,P<0.05)。A组小鼠的临床评分也比B组小鼠更严重(1.69±1.12 vs 0.35±0.67,P<0.01)。C组小鼠未发生EAMG。B组小鼠脾脏和淋巴结中Cbl的mRNA表达低于A组小鼠,但均高于C组小鼠(P<0.05)。B组小鼠Cbl的mRNA表达高于A组小鼠(P<0.05)。
Tα146 - 162 - iMDCs可预防EAMG,可能是通过Cbl对BCR信号的负调控实现的。