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Poly dispersed acid-functionalized single walled carbon nanotubes target activated T and B cells to suppress acute and chronic GVHD in mouse model.
Immunology Letters ( IF 3.3 ) Pub Date : 2020-06-03 , DOI: 10.1016/j.imlet.2020.05.006
Md Babu Mia 1 , Rajiv K Saxena 1
Affiliation  

Graft versus host disease (GVHD) results from hyper-activation of transplanted lymphocytes against the host antigens. Bone marrow transplantation in humans as well as some cases of blood transfusion and organ transplantation are associated with a strong GVH reaction resulting in GVHD that in many cases may be fatal. We had previously shown that poly-dispersed acid-functionalized single-walled carbon nanotubes (AF-SWCNTs) specifically target activated T and B lymphocytes and kill them. In the present study, efficacy of AF-SWCNTs to suppress the GVH reaction was tested in the mouse model. Acute GVHD was induced in mice by administering intravenously 30 or 60 million spleen cells from a parental strain (C57bl/6 mouse, MHC haplotype H-2b) to host (C57bl/6 x Balb/c) F1 mice (MHC haplotype H-2b/d)and waiting for 8–10 days. Chronic GVHD was similarly induced by administration of 30 million parent spleen cells to F1 mice and waiting for a period of 60 days. Our results demonstrate a marked decline in splenomegaly and recovery of spleen T (both CD4 and CD8) and B cells in GVHD mice treated with AF-SWCNTs. AF-SWCNTs treatment also limited T and B cell proliferation by restricting S-phage of cell cycle. Generation of anti-host cytotoxic T cells (CTLs) was also markedly suppressed by AF-SWCNT treatment of acute GVHD mice, and a significant reduction in the generation of anti-host antibodies could also be demonstrated. Taken together, our results suggest that the AF-SWCNTs can be considered as a potential therapeutic agent for treating GVHD.



中文翻译:

多分散的酸官能化的单壁碳纳米管靶向激活的T细胞和B细胞,以抑制小鼠模型中的急性和慢性GVHD。

移植物抗宿主病(GVHD)是由于移植的淋巴细胞针对宿主抗原的过度活化而导致的。人的骨髓移植以及某些输血和器官移植病例与强烈的GVH反应有关,导致GVHD在许多情况下可能是致命的。先前我们已经证明,多分散的酸官能化的单壁碳纳米管(AF-SWCNT)专门针对活化的T和B淋巴细胞并杀死它们。在本研究中,在小鼠模型中测试了AF-SWCNT抑制GVH反应的功效。通过将来自亲本品系(C57bl / 6小鼠,MHC单体型H- 2b)的30或6000万脾细胞静脉内给予宿主(C57bl / 6 x Balb / c)F1小鼠(MHC单体型H- 2天/天)并等待8-10天。慢性GVHD类似地是通过向F1小鼠施用3000万亲本脾细胞并等待60天来诱导的。我们的结果表明,用AF-SWCNTs处理的GVHD小鼠脾肿大明显减少,脾T(CD4和CD8)和B细胞恢复正常。AF-SWCNTs治疗还通过限制细胞周期的S-噬菌体来限制T细胞和B细胞的增殖。AF-SWCNT处理急性GVHD小鼠也显着抑制了抗宿主细胞毒性T细胞(CTL)的产生,并且还可以证明抗宿主抗体的产生显着减少。综上所述,我们的结果表明AF-SWCNT可以被认为是治疗GVHD的潜在治疗剂。

更新日期:2020-06-03
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