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The effects of CTX damage or inhibition of bone marrow hematopoiesis and GM-CSF stimulation of bone marrow hematopoiesis on the peripheral blood TCRβ CDR3 repertoire of BALB/c mice.
Immunopharmacology and Immunotoxicology ( IF 3.3 ) Pub Date : 2020-02-18 , DOI: 10.1080/08923973.2020.1728309
Liwen Yang 1 , Fangfang Duan 1 , Danhua Su 1 , Yuehong Li 1 , Long Ma 1 , Bin Shi 2 , Xiaoyan He 1 , Rui Ma 1 , Chenbo Ding 1 , Suhong Sun 3 , Xinsheng Yao 1
Affiliation  

Objective: This paper aims to investigate the dynamic changes of the T-cell receptor (TCR) β complementarity-determining region 3 (CDR3) repertoire during cyclophosphamide or Cytoxan (CTX) damage or inhibition of bone marrow hematopoiesis caused by a reduction of peripheral blood white blood cells (WBCs) in BALB/c mice.Methods: We analyze TCR CDR3 repertoire of BALB/c mice including (1) NS control group (2) CTX damage group (3) CTX damage + GM-CSF recovery group (4) CTX damage + auto-recovery group.Results: The number of WBCs in the CTX group is significantly lower than that in the NS group and after GM-CSF injection, the GM-CSF group is higher than that in the NS group. The diversity of the CTX damage group is the highest and there is a significant difference in high-frequency clonal proliferation between the CTX damage group and CTX damage + GM-CSF recovery group compared with the NS control group. In addition, the numbers of unique productive CDR3 overlapping numbers in the four experimental groups are similar.Conclusions: These data reveal that CTX significantly reduced the number of WBCs and ratio of high-frequency TCR CDR3 sequences, and indirectly increased the diversity of the TCR CDR3 repertoire. GM-CSF quickly restored the number of WBCs, and partially restored changes in the TCR CDR3 repertoire induced by CTX. Results from monitoring the dynamic changes of the TCR CDR3 repertoire can be used to assess the effects of CTX and GM-CSF on the function of peripheral blood T cells and to explore the possible underlying mechanisms.

中文翻译:

CTX损伤或抑制骨髓造血和GM-CSF刺激骨髓造血对BALB / c小鼠外周血TCRβCDR3的影响。

CTX损伤组的多样性最高,与NS对照组相比,CTX损伤组和CTX损伤+ GM-CSF恢复组之间的高频克隆增殖存在显着差异。此外,四个实验组中独特的生产性CDR3重叠数的数量相似。结论:这些数据表明,CTX显着减少了WBC的数量和高频TCR CDR3序列的比率,并间接增加了TCR的多样性CDR3曲目。GM-CSF快速恢复了WBC的数量,并部分恢复了CTX诱导的TCR CDR3库的变化。
更新日期:2020-04-20
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