The effects of CAMPATH-1H on cell viability do not correlate to the CD52 density on the cell surface.

The effects of CAMPATH-1H on cell viability do not correlate to the CD52 density on the cell surface.
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DOI:
10.1371/journal.pone.0103254
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Saudemont A
Saudemont A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lee F;Luevano M;Veys P;Yong K;Madrigal A;Shaw BE;Saudemont A

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移植物抗宿主病(GvHD)是造血干细胞移植(HSCT)后的主要并发症之一。campaign - 1h用于移植前调理方案,通过靶向T细胞上的CD52抗原导致其耗竭,有效降低GvHD。关于CD52表达和campaign - 1h对免疫细胞影响的信息很少,而且仅限于外周血(PB) T和B细胞。迄今为止,campaign - 1h对脐带血(CB)细胞的影响尚未得到研究。本研究旨在分析CD52的表达以及campaign - 1h对新鲜或冷冻、静息或活化、PB单核细胞(PBMC)和CB单核细胞(CBMC)的影响。静息状态下,除自然杀伤(NK)细胞CD52水平在PB(421.0±9.857)高于CB(334.3±9.559)外,CB中CD52表达高于PB T细胞亚群(653.66±26.68 vs 453.32±19.2)和B细胞(622.2±20.65 vs 612.0±9.101)。相比之下,激活后所有细胞类型的CD52水平具有可比性。campaign - 1h比活化细胞更有效地消耗静息细胞,观察到约80-95%的凋亡和低水平的坏死。细胞表面CD52密度与campaign - 1h的消耗作用无直接关系。此外,使用不同浓度的campaign - 1h对细胞活力没有影响。CD52未在HSC上表达,但随着细胞分化开始表达,提示campaign - 1h可能影响HSC的分化和增殖。我们的研究提供了有见地的信息,这有助于更好地理解在HSCT中使用campaign - 1h作为调节方案的一部分。
Graft versus host disease (GvHD) is one of the main complications after hematological stem cell transplantation (HSCT). CAMPATH-1H is used in the pre-transplant conditioning regimen to effectively reduce GvHD by targeting CD52 antigens on T cells resulting in their depletion. Information regarding CD52 expression and the effects of CAMPATH-1H on immune cells is scant and limited to peripheral blood (PB) T and B cells. To date, the effects of CAMPATH-1H on cord blood (CB) cells has not been studied. Here we aimed to analyze CD52 expression and the effects of CAMPATH-1H on fresh or frozen, resting or activated, PB mononuclear cells (PBMC) and CB mononuclear cells (CBMC). In resting state, CD52 expression was higher in CB than PB T cell subsets (653.66±26.68 vs 453.32±19.2) and B cells (622.2±20.65 vs 612.0±9.101) except for natural killer (NK) cells where CD52 levels were higher in PB (421.0±9.857) than CB (334.3±9.559). In contrast, CD52 levels were comparable across all cell types after activation. CAMPATH-1H depleted resting cells more effectively than activated cells with approximately 80–95% of apoptosis observed with low levels of necrosis. There was no direct correlation between cell surface CD52 density and depleting effects of CAMPATH-1H. In addition, no difference in cell viability was noted when different concentrations of CAMPATH-1H were used. CD52 was not expressed on HSC but began to be expressed as the cells differentiate, implying that CAMPATH-1H could potentially affect HSC differentiation and proliferation. Our study provides insightful information, which contributes to the better understanding in the use of CAMPATH-1H as part of the conditioning regime in HSCT.
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