Published November 18, 2025 | Version v1
Dataset Open

Comparison of CD4 T cell response in Plasmodium falciparum and vivax malaria

Authors/Creators

  • 1. Burnet Institute
  • 2. ROR icon QIMR Berghofer Medical Research Institute
  • 3. Monash University, School of Translational Medicine
  • 4. Papuan Health and Community Development Foundation
  • 5. ROR icon Menzies School of Health Research
  • 6. Centre for Tropical Medicine and Global Health, University of Oxford, Oxford,
  • 7. Mahidol-Oxford Tropical Medicine Research Unit
  • 8. ROR icon Charles Darwin University
  • 9. University of Melbourne, Department of Infectious Diseases
  • 10. Monash University, School of Translational Medicine,

Description

Plasmodium falciparum and P. vivax are parasites responsible for most malaria cases globally. In areas where these species co-exist, individuals gain protection from P. vivax more rapidly, and important biological differences between species may impact the immune response. CD4 T cells are key drivers of immunity to malaria, both as effector and helper cells, with T-follicular helper (Tfh) cells having key roles in antibody development. Comparative studies on CD4 T cell responses between these species are limited.  

Methods: We assessed CD4 T cells in adults with either P. falciparum or P. vivax malaria. Activation and proliferation of CD4 T cells were measured ex vivo, and functional capacity determined by intracellular cytokine staining by flow cytometry.  

Results: The phenotype, activation and proliferation of CD4 T cells and effector CD4 T cell subsets were comparable between species. However, within the peripheral (p)Tfh cell compartment, there was some evidence for species specific activation with a relative increased a skew towards pTfh1 cells in P. falciparum infection, and pTfh2 cells in P. vivax. Additionally, in P. falciparum, increased IL-10 production was detected, including within IL-21 producing CD4 T cells.  

Conclusion: While activation and function of CD4 T cells in malaria are largely comparable, some species-dependent responses are detected within the pTfh cell compartment that may impact antibody development.

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