Nalubega M.Soon M.S.F.Andrew D.Ortega-Pajares A.Canning J.Dooley N.Loughland J.R.Engwerda C.Kenangalem E.Price R.N.Minigo G.Anstey N.M.Oyong D.A.Boyle M.J.Mahidol University2026-05-112026-05-112026-04-15Journal of Infectious Diseases Vol.233 No.4 (2026) , e891-e90100221899https://repository.li.mahidol.ac.th/handle/123456789/116657Background: Plasmodium falciparum and vivax are parasites responsible for most malaria cases globally. In areas where these species coexist, individuals gain protection from P vivax more rapidly, and important biological differences between species may affect immune responses. CD4 T cells are key drivers of immunity to malaria as effector and helper cells, with T follicular helper 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 was determined by intracellular cytokine staining via flow cytometry. Results: The phenotype, activation, and proliferation of CD4 T cell subsets were largely comparable between species. However, within the peripheral T follicular helper (pTfh) cell compartment, there was some evidence for species-dependent activation, with relatively increased pTfh1 cells in P falciparum infection. Additionally, in P falciparum, increased IL-10 production was detected, including within IL-21–producing CD4 T cells. Conclusions: 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 affect antibody development.MedicineArticleSCOPUS10.1093/infdis/jiag1152-s2.0-1050376551751537661341757944