Poster Presentation First Malaria World Congress 2018

Enhanced functional activity and long-term transcriptional changes in memory γδ T cells following malaria infection. (#430)

Rasika Kumarasingha 1 2 , Lisa J Ioannidis 1 2 , Waruni Abeysekera 1 2 , Dinidu Wijesurendra 1 2 , Ramin Mazhari 1 2 , Daniel P Poole 3 4 , Diana S Hansen 1 2 , Louis Schofield 1 5 , Emily M Eriksson 1 2
  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia
  3. Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia
  4. Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, Australia
  5. James Cook University, Cairns, QLD, Australia

Aims: γδ T cells play an essential role in the immune response to malaria infection. However, potential γδ T cell memory responses upon re-encounter with malaria antigens have not been evaluated extensively. This study focused on determining the functional capacity and transcriptional changes in malaria pre-exposed γδ T cells in malaria mouse models.

Methods: We used a Plasmodium chabaudi infection model, which results in non-lethal, self-resolving infections in C57BL/6 mice. All mice were drug-treated with chloroquine and pyrimethamine on day 14 to clear the infections. This was after peak parasitemia had occurred and the mice were almost completely recovered. Twelve weeks after completion of drug-treatment, liver and spleen-derived γδ T cells were stimulated with Plasmodium-infected red blood cells in vitro.

Results: The frequency of γδ T cells that produced IFNγ and displayed cytotoxic activity was significantly higher in previously infected mice compared to γδ T cells from naïve mice. Phenotypic analysis showed that the responding γδ T cells expressed CD44, but lacked CD62L expression corresponding to an effector memory phenotype (EM). These EM γδ T cells were FACS sorted and transcriptional analysis was performed. Differential expression was assessed relative to a fold change threshold of 1.5. Pre-exposed γδ T cells had a total of 213 differentially expressed (DE) genes compared to naïve γδ T cells of which 98 genes were upregulated and 115 genes downregulated. The chemokines CCL3 and CCL4, and IFNγ were among the top 75 DE genes.

Conclusions: Prior exposure to malaria leads to γδ T cells with enhanced response capacity and long-term transcriptional changes.


This work was supported by NMHRC grant # APP1067222