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bioRxiv · 10.1101/2025.04.28.651092

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

Abstract

BackgroundPlasmodium 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) having key roles in antibody development. Comparative studies on CD4 T cell responses between these species are limited. MethodsWe 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. ResultsThe 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 evidence for a skew towards pTfh1 cells in P. falciparum, and pTfh2 cells in P. vivax. Additionally, in P. falciparum, increased IL-10 production was detected, including within IL-21 producing CD4 T cells. ConclusionWhile 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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Nalubega, M., Soon, M. S., Andrew, D., Dooley, N., Loughland, J., Engwerda, C., Kenangalem, E., Price, R. N., Minigo, G., Anstey, N. M., Oyong, D., Boyle, M. J.. 2025-04-29. Comparison of CD4 T cell response in Plasmodium falciparum and vivax malaria. https://doi.org/10.1101/2025.04.28.651092

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