Effect of cyclosporine and tacrolimus on the growth of Epstein-Barr virus-transformed B-cell lines.

Effect of cyclosporine and tacrolimus on the growth of Epstein-Barr virus-transformed B-cell lines.
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环孢素和他克莫司对 Epstein-Barr 病毒转化的 B 细胞系生长的影响。

DOI:
10.1097/00007890-199805150-00017
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发表时间:
1998
期刊:
影响因子:
6.2
通讯作者:
Martinez,OM
Martinez,OM
中科院分区:
医学2区
文献类型:
--
作者:
Beatty,PR;Krams,SM;Esquivel,CO;Martinez,OM

文献摘要

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背景:接受免疫抑制药物的移植患者发生EB病毒相关疾病(包括移植后淋巴组织增生性疾病)的风险增加。T淋巴细胞的功能对于防止EBV感染的B细胞的扩增至关重要,其被免疫抑制药物抑制。本研究的目的是确定免疫抑制药物是否对EBV感染的B细胞有直接的作用。方法:在有或没有环孢霉素(CsA)和他克莫司(TAC)的情况下培养EBV感染的自发性淋巴母细胞系(SLCL),通过3-甲基-β-D-半乳糖苷酶(β-D-半乳糖苷酶)测定其生长和增殖。(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物和[3 H]胸苷掺入测定。台盼蓝计数法检测CsA和TAC对SLCL细胞活力的影响。SLCLs的凋亡诱导与抗Fas激动剂的单克隆抗体在CsA和TAC的存在或不存在下,并通过流式细胞术后末端脱氧核苷酸转移酶末端标记和碘化丙啶staining.Results。CsA和TAC,但不是西罗莫司,增加SLCLs的生长。在CsA和TAC存在下的生长增加归因于SLCL的细胞活力增强而不是细胞分裂增加。此外,CsA和TAC抑制Fas介导的SLCLs.Conclusions凋亡。CsA和TAC增强EBV转化的B细胞系的存活。CsA和TAC通过防止细胞死亡促进或增强SLCL生长,但不影响细胞分裂。CsA和TAC对细胞死亡的抑制可能有助于免疫抑制个体中EBV感染细胞的扩增。
Background.Transplant patients receiving immunosuppressive drugs are at increased risk for Epstein-Barr virus (EBV)-associated disorders including posttransplant lymphoproliferative disorder. The function of T lymphocytes, which are critical to preventing the expansion of EBV-infected B cells, is inhibited by immunosuppressive drugs. The purpose of this study was to determine whether immunosuppressive drugs have direct effects on EBV-infected B cells.Methods.The growth and proliferation of EBV-infected spontaneous lymphoblastoid cell lines (SLCLs), cultured in the presence or absence of cyclosporine (CsA) and tacrolimus (TAC), were measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and [3 H] thymidine incorporation assays. The effect of CsA and TAC on the viability of SLCLs was determined by cell counts with trypan blue. Apoptosis of SLCLs was induced with an anti-Fas agonist monoclonal antibody in the presence or absence of CsA and TAC and measured by flow cytometry after terminal deoxynucleotidyl transferase end-labeling and propidium iodide staining.Results.CsA and TAC, but not sirolimus, increased the growth of SLCLs. The increased growth in the presence of CsA and TAC was attributable to enhanced cell viability and not increased cell division of SLCLs. In addition, CsA and TAC inhibited Fas-mediated apoptosis of SLCLs.Conclusions.CsA and TAC enhance the survival of EBV-transformed B-cell lines. CsA and TAC promote or augment SLCL growth through protection from cell death but do not affect cell division. The inhibition of cell death by CsA and TAC may contribute to the expansion of EBV-infected cells in immunosuppressed individuals.