Journal of Shandong University (Health Sciences) ›› 2018, Vol. 56 ›› Issue (7): 1-6.doi: 10.6040/j.issn.1671-7554.0.2017.981

   

Impact of CDK9 inhibition for T cells on TLR5-targeting monitoring during allorejection

LI Xiaomei, LIANG Ting, ZHANG Chao, CAO Hui, HOU Guihua   

  1. Biomedical Isotope Research Center, Basic Science of Medical School, Shandong University, Jinan 250012, Shandong, China
  • Published:2022-09-27

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Abstract: Objective To explore the impact of T cells Cyclin-dependent kinase 9(CDK9)inhibition on Toll-like receptor 5(TLR5)targeting monitoring of acute allorejection. Methods 125I-anti-TLR5 was prepared with Iodogen method. Label rate, stability and cell uptake and dissociation between spleen cells and 125I-anti-TLR5 were analyzed. Allografted-SCID mouse models were established through T cells adoptive transferred and were divided into control group and CDK9 inhibition group. Another group of mice were injected with 125I-anti-TLR5 before injection of unlabeled anti-TLR5 antibody(100 μL 10 mg/kg body weight)as a blocking group. Allograft survival and graft histopathology were observed. 125I-anti-TLR5 was injected through tail vein at the peak of the control group rejection, and the biodistribution and whole-body phosphor-autoradiography were analyzed. Results T cells CDK9 inhibition apparently prolonged allograft survival from(20.00±1.58)d to(28.20±2.77)d, and weaken inflammation and increased expression of TLR5 on allografts. 125I-anti-TLR5 was prepared successfully with high label rate(96.2%)and stability(>90% at 72 h). 山 东 大 学 学 报 (医 学 版)56卷7期 -李晓梅,等.抑制T细胞CDK9对TLR5靶向监测同种异体移植排斥的影响 \=-Recipient spleen cells-pretreated with CDK9 inhibitor increased the uptake ratio of 125I-anti-TLR5 and reduced the dissociating ratio(P<0.05). Ex vivo biodistribution studies revealed that 125I-anti-TLR5 could be accumulated in skin allograft. T/NT ratio(allograft/ oposite skin)of CDK9 inhibition group was higher than that of control group(3.70±0.16 vs 2.02±0.06)at 72 h post injection. Whole-body phosphor-autoradiography imaging showed that clear graft localization was developed at 48 h, lasting longer in CDK9 inhibition group than control group, and no obvious accumulating imaging was noted in blocked group. Conclusion The inhibition of CDK9 on T cells can prolong allograft survival through reducing inflammation and promoting the expression of TLR5 of allograft, which may favor in vivo monitoring of TLR5 targeting acute allorejection.

Key words: Iodine 125, Toll-like receptor 5, Cyclin-dependent kinase 9, Phosphor auto-radio imaging, Allotransplantation

CLC Number: 

  • R817.33
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