Longitudinal Analysis of the Human T Cell Response during Acute Hantavirus Infection
Longitudinal Analysis of the Human T Cell Response during Acute Hantavirus Infection
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DOI：
10.1128/jvi.05548-11
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发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Bjorkstrom, Niklas K.
中科院分区：
文献类型：
--
作者：
Lindgren, Therese;Ahlm, Clas;Bjorkstrom, Niklas K.
在人类病毒感染期间对T细胞免疫应答的纵向研究对于我们理解效应T细胞应答如何发展、清除感染和提供持久免疫力至关重要。在这里，在普马拉汉坦病毒感染的人群中爆发后，我们纵向分析了感染个体从首次出现临床症状直到病毒清除的主要CD 8 T细胞反应。在临床症状发作后早期观察到强烈的CD 8 T细胞应答，这通过大量Ki 67（+）CD 38（+）HLA-DR（+）效应CD 8 T细胞的存在来确定。这种反应包括高达50%的总血液CD 8 T细胞，随后与病毒载量的减少平行收缩。穿孔素和颗粒酶B的表达水平在整个初始T细胞应答中是高的，并且在病毒清除后同样正常化。当监测调节组分时，在感染期间在患者中未观察到调节性CD 4或CD 8 T细胞的诱导。然而，CD 8以及CD 4 T细胞表现出抑制性PD-1和CTLA-4分子的不同表达谱。目前的结果提供了深入了解人类T细胞反应的发展，从病毒感染后的临床症状的发作到疾病的解决。
Longitudinal studies of T cell immune responses during viral infections in humans are essential for our understanding of how effector T cell responses develop, clear infection, and provide long-lasting immunity. Here, following an outbreak of a Puumala hantavirus infection in the human population, we longitudinally analyzed the primary CD8 T cell response in infected individuals from the first onset of clinical symptoms until viral clearance. A vigorous CD8 T cell response was observed early following the onset of clinical symptoms, determined by the presence of high numbers of Ki67(+)CD38(+)HLA-DR(+) effector CD8 T cells. This response encompassed up to 50% of total blood CD8 T cells, and it subsequently contracted in parallel with a decrease in viral load. Expression levels of perforin and granzyme B were high throughout the initial T cell response and likewise normalized following viral clearance. When monitoring regulatory components, no induction of regulatory CD4 or CD8 T cells was observed in the patients during the infection. However, CD8 as well as CD4 T cells exhibited a distinct expression profile of inhibitory PD-1 and CTLA-4 molecules. The present results provide insight into the development of the T cell response in humans, from the very onset of clinical symptoms following a viral infection to resolution of the disease.