不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:B cells do not play a role in vaccine-mediated immunity against Marek's disease.
B cells do not play a role in vaccine-mediated immunity against Marek's disease.
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研究表明,B 细胞在 MD 疫苗介导的免疫中并不发挥关键作用。
马立克氏病病毒(MDV)是一种高度致瘤的α-疱疹病毒,是鸡马立克氏病(MD)的病原体。疫苗诱导的针对MD的抗病毒免疫活性可降低早期溶细胞感染水平、羽毛毛囊上皮细胞(FFE)中无细胞病毒粒子的产生以及淋巴瘤形成。尽管几种疫苗的成功已大大减少了MD造成的经济损失,但疫苗诱导免疫的机制仍知之甚少。
为深入了解B细胞在疫苗介导保护中可能的作用,我们在雏鸡出壳当日进行法氏囊切除,并于8天后接种疫苗。接种后10天进行攻毒,攻毒前部分鸡只接受来自同龄对照鸡的过继淋巴细胞,部分未接受。研究还包括接种/攻毒和未接种/攻毒的完整鸡只。法氏囊切除后进行了两次PBMN细胞的流式细胞术分析,以确认B细胞耗竭并评估手术对T细胞群体的影响。在试验终止时对皮肤样本进行免疫组化分析和病毒基因组拷贝数评估,以测定攻毒鸡只皮肤组织FFE中MDV的复制速率。
未接种疫苗/攻毒的鸡出现了典型的MD临床症状,而接种疫苗/攻毒组以及切除腔上囊的接种疫苗/攻毒组,无论是否过继转移淋巴细胞,均获得完全保护,无短暂性瘫痪、体重减轻或T细胞淋巴瘤的迹象。皮肤样本的免疫组织化学分析和病毒基因组拷贝数评估显示,与接种疫苗/攻毒鸡不同,未接种疫苗/攻毒鸡在终止时FFE中产生了大量病毒颗粒。在切除腔上囊的接种疫苗/攻毒组中,仅在攻毒前接受过继淋巴细胞的鸡皮肤中检测到少量复制型病毒粒子。
Marek's disease virus (MDV), a highly oncogenic α-herpesvirus, is the etiological agent of Marek's disease (MD) in chickens. The antiviral activity of vaccine-induced immunity against MD reduces the level of early cytolytic infection, production of cell-free virions in the feather follicle epithelial cells (FFE), and lymphoma formation. Despite the success of several vaccines that have greatly reduced the economic losses from MD, the mechanism of vaccine-induced immunity is poorly understood.
To provide insight into possible role of B cells in vaccine-mediated protection, we bursectomized birds on day of hatch and vaccinated them eight days later. The birds were challenged 10 days post vaccination with or without receiving adoptive lymphocytes from age-matched control birds prior to inoculation. The study also included vaccinated/challenged and non-vaccinated challenged intact birds. Flowcytometric analysis of PBMN cells were conducted twice post bursectomy to confirm B cell depletion and assess the effect of surgery on T cell population. Immunohistochemical analysis and viral genome copy number assessment in the skin samples at termination was performed to measure the replication rate of MDV in the FFE of the skin tissues of the challenged birds.
The non-vaccinated/challenged birds developed typical clinical signs of MD while the vaccinated/challenged and bursectomized, vaccinated/challenged groups with or without adoptive lymphocyte transfer, were fully protected with no sign of transient paralysis, weight loss, or T cell lymphomas. Immunohistochemical analysis and viral genome copy number evaluation in the skin samples revealed that unlike the vaccinated/challenged birds a significant number of virus particles were produced in the FFE of the non-vaccinated/challenged birds at termination. In the bursectomized, vaccinated/challenged groups, only a few replicating virions were detected in the skin of birds that received adoptive lymphocytes prior to challenge.
The study shows that B cells do not play a critical role in MD vaccine-mediated immunity.
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