CD38+ T cells in malaria immuno-suppression

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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.