CD38+ T cells in malaria immuno-suppression

疟疾的特点是T细胞反应有缺陷，特别是T细胞生长受抑。T细胞对预防疟疾至关重要，免疫反应缺陷很可能有利于这种寄生虫。我们想找出疟疾中免疫反应是如何关闭的，这样我们就可以对此做些什么，并帮助抗击寄生虫。疟疾每年导致200多万儿童死亡，目前还没有有效的疫苗。我们有两条重要的线索，即在疟疾感染期间，可能发生了什么导致T细胞生长受抑。首先，我们发现在感染过程中，表达一种名为CD38的表面分子的T细胞大量增加。这些细胞的增加与动物T细胞生长能力的下降相关。事实上，其他研究人员已经观察到，在小鼠体内，CD38T细胞可以抑制免疫。其次，我们假设它们可能是急性疟疾期间观察到的T细胞反应性受损的原因，以及生活在不断被寄生虫感染的地区的人类免疫反应普遍较差的原因。事实上，当我们从这些人的血细胞中取出表达CD38的细胞后，这些细胞就“恢复”了，并且能够在我们的检测中生长得更好。因此，我们认为CD38T细胞是疟疾免疫抑制的重要介体。我们现在想要了解寄生虫是如何诱导这些CD38T细胞的，以及它们抑制T细胞反应的能力如何使寄生虫受益。认识到这一点，我们的目标是开发能够避免被疟疾关闭的疫苗。在癌症和急性病毒性疾病中，表达CD38的T细胞也增加，如晚期艾滋病毒。了解它们在疟疾中的作用也将为我们提供抗击此类疾病的新线索。

Malaria is characterised by defective T cell responses, particularly suppressed T cell growth. T cells are critical to malaria protection and defective immune responses are likely to benefit the parasite. We want to find out how immune-responses are turned off in malaria, so that then we can do something about this, and help fight off the parasite. Malaria kills over 2 million children each year and there is no effective vaccine. We have two important clues as what may be happenning to cause suppressed T cell growth during malaria infection. Firstly, we found a massive increase in T cells expressing a surface molecule called CD38 duirng infection. Increases in these cells correlated with decreases in the ability of the T cells from the animals to grow. Indeed, other researchers had observed that in mice CD38 T cells can suppress immunity. Secondly, we hypothesized that they may be responsible for the impaired T cell reactivity observed during acute malaria, and the general poor state of immune responses in humans living in areas where they are being constantly infected by the parasite. Indeed, when we removed cells expressing CD38 from blood cells from such individuals, these 'recovered' and were able to grow much better in our assays. Therefore we propose that CD38 T cells are importnat mediators of malaria immuno-suppression. We now want to understand how the parasite induces these CD38 T cells, and how their ability to suppress T cell responses can benefit the parasite. Knowing this we aim to develop vaccines which can avoid being turned off by malaria. T cells expressing CD38 are also increased in cancer and acute viral disease, such as late stage HIV. Understanding their role in malaria will also give us new clues to fight such diseases.