SIVmac239感染的恒河猴中T淋巴细胞凋亡动力学及细胞免疫反应
Kinetics of T lymphocyte apoptosis and the cellular immune response in SIVmac239-infected rhesus macaques.
作者信息
Meythaler Mareike, Pryputniewicz Sarah, Kaur Amitinder
机构信息
Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, MA, USA.
出版信息
J Med Primatol. 2008 Dec;37 Suppl 2(Suppl 2):33-45. doi: 10.1111/j.1600-0684.2008.00323.x.
BACKGROUND
Although increased apoptosis is a central feature of AIDS, little is known about its kinetics or relationship to the early host response in acute HIV/SIV infection.
METHODS
Ex vivo apoptosis in freshly isolated peripheral blood and lymph node lymphocytes was monitored longitudinally in SIVmac239-infected rhesus macaques by flow-cytometric detection of active caspase-3, cleaved poly (ADP-ribose) polymerase, and fragmented DNA.
RESULTS
Increased apoptosis of multiple lymphocyte subsets was observed in the first 2 weeks following SIV infection. Apoptosis of CD4+ T lymphocytes was of low magnitude but peaked earlier than other T lymphocyte subsets. A 10- to 36-fold increase in CD8+ T lymphocyte apoptosis coincided temporally with onset of the SIV-specific cellular immune response and enrichment of caspase-3-positive cells within recently proliferating, activated CD8+ T lymphocytes.
CONCLUSIONS
The virus-specific T lymphocyte response to primary infection and generalized non-specific immune activation contribute to the pathogenesis of apoptosis in acute SIV infection.
背景
虽然细胞凋亡增加是艾滋病的一个核心特征，但对于其动力学或与急性HIV/SIV感染早期宿主反应的关系却知之甚少。
方法
通过流式细胞术检测活性半胱天冬酶-3、裂解的聚（ADP-核糖）聚合酶和片段化DNA，对感染SIVmac239的恒河猴新鲜分离的外周血和淋巴结淋巴细胞中的体外细胞凋亡进行纵向监测。
结果
在SIV感染后的前2周内观察到多个淋巴细胞亚群的细胞凋亡增加。CD4+T淋巴细胞的细胞凋亡程度较低，但比其他T淋巴细胞亚群更早达到峰值。CD8+T淋巴细胞凋亡增加10至36倍，在时间上与SIV特异性细胞免疫反应的开始以及最近增殖、活化的CD8+T淋巴细胞内半胱天冬酶-3阳性细胞的富集相吻合。
结论
病毒特异性T淋巴细胞对原发性感染的反应和全身性非特异性免疫激活促成了急性SIV感染中细胞凋亡的发病机制。
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