CD38+ T cells in malaria immuno-suppression

疟疾的特征是T细胞反应缺陷，特别是T细胞生长受到抑制。T细胞对疟疾保护至关重要，而有缺陷的免疫反应可能会使寄生虫受益。我们想知道疟疾中免疫反应是如何被关闭的，这样我们就可以做些什么，帮助对抗寄生虫。疟疾每年造成200多万儿童死亡，而且没有有效的疫苗。我们有两个重要的线索，可能是什么原因导致疟疾感染期间T细胞生长受到抑制。首先，我们发现在感染过程中，T细胞表达一种称为CD38的表面分子的数量大量增加。这些细胞的增加与动物T细胞生长能力的降低相关。事实上，其他研究人员已经观察到，在小鼠中，CD38 T细胞可以抑制免疫力。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的普遍不良状态。事实上，当我们从这些个体的血细胞中去除表达CD38的细胞时，这些细胞“恢复”并能够在我们的测定中更好地生长。因此，我们认为CD38 T细胞是疟疾免疫抑制的重要介质。我们现在想了解寄生虫如何诱导这些CD38 T细胞，以及它们抑制T细胞反应的能力如何使寄生虫受益。了解到这一点，我们的目标是开发可以避免被疟疾关闭的疫苗。表达CD38的T细胞在癌症和急性病毒性疾病中也会增加，如晚期HIV。了解它们在疟疾中的作用也将为我们防治此类疾病提供新的线索。

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.