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巴厘岛牛实验感染牛瘟病毒后淋巴细胞亚群动力学的流式细胞术分析

Flow cytometric analysis of lymphocyte subset kinetics in Bali cattle experimentally infected with Jembrana disease virus.

作者信息

Tenaya I W Masa, Heel Kathy, Stumbles Philip A, Wilcox Graham E

机构信息

School of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, WA 6150, Australia.

出版信息

Vet Immunol Immunopathol. 2012 Oct 15;149(3-4):167-76. doi: 10.1016/j.vetimm.2012.06.013. Epub 2012 Jun 18.

Abstract

Jembrana disease virus (JDV) is an unusual bovine lentivirus that causes an acute and sometimes fatal disease after a short incubation period in Bali cattle (Bos javanicus). The pathological changes occur primarily in lymphoid tissues, which feature proliferating lymphoblastoid-like cells predominantly throughout parafollicular (T-cell) areas, and atrophy of follicles (B-cell) areas. Five Bali cattle were experimentally infected with JDV and all developed typical clinical signs of Jembrana disease characterised by a transient febrile response, enlargement of superficial lymph nodes and a significant leukopenia. Flow cytometric analysis of PBMC during the acute (febrile) disease phase showed that the reduced number of lymphocytes was due to a significant decrease in both the proportion and absolute numbers of CD4(+) T cells, but not CD8(+) T-cells or CD21(+) B-cells. At the end of the febrile phase, total numbers of both CD8(+) T-cells and CD21(+) B-cells increased significantly, while CD4(+) T-cell numbers remained below normal values, resulting in a significantly reduced CD4(+):CD8(+) ratio. We speculate that the persistent depletion of CD4(+) T cells following JDV infection, through lack of CD4(+) T cell help to B cells, may explain the lack of production of JDV-specific antibodies for several weeks after recovery despite an increase in CD21(+) B cell numbers. Further, our previous data showing that IgG(+) plasma cells are targets for JDV infection, correlated with our current data demonstrating an increase in CD8(+) T cell numbers, supports the suggestion that anti-viral cytotoxic T cell or other cell-mediated immune responses may be critical in the recovery process, although this remains to be formally demonstrated for JDV.

摘要

杰姆纳纳病病毒(JDV)是一种不同寻常的牛慢病毒,在巴厘牛(爪哇野牛)中经过短暂潜伏期后会引发一种急性且有时致命的疾病。病理变化主要发生在淋巴组织,其特征是在整个滤泡旁(T细胞)区域主要有增殖的淋巴母细胞样细胞,以及滤泡(B细胞)区域萎缩。五头巴厘牛经实验感染了JDV,所有牛都出现了杰姆纳纳病的典型临床症状,其特征为短暂发热反应、浅表淋巴结肿大和显著的白细胞减少。在急性(发热)疾病阶段对外周血单核细胞进行流式细胞术分析表明,淋巴细胞数量减少是由于CD4(+) T细胞的比例和绝对数量均显著下降,而CD8(+) T细胞或CD21(+) B细胞则没有。在发热阶段结束时,CD8(+) T细胞和CD21(+) B细胞的总数均显著增加,而CD4(+) T细胞数量仍低于正常值,导致CD4(+):CD8(+) 比值显著降低。我们推测,JDV感染后CD4(+) T细胞持续耗竭,由于缺乏CD4(+) T细胞对B细胞的辅助,可能解释了康复后数周内尽管CD21(+) B细胞数量增加但仍未产生JDV特异性抗体的原因。此外,我们之前的数据表明IgG(+)浆细胞是JDV感染的靶标,这与我们目前证明CD8(+) T细胞数量增加的数据相关,支持了抗病毒细胞毒性T细胞或其他细胞介导的免疫反应可能在恢复过程中起关键作用的观点,尽管这一点尚未在JDV中得到正式证实。

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