Here, the use of high-dimensional single-cell mass cytometry allowed us to identify specific subsets of memory CD4+ T cells and MBCs expressing the TH1-defining transcription factor T-bet, associated with either increased or reduced risk of P. vivax infection, demonstrating that IFN-γ–driven responses to malaria support the development of diverse responses that have the potential to give rise to different infection outcomes. This evidence concerns the gene IFNG and infection.