Longitudinal study of changes in γδ T cells and CD4+ T cells upon asymptomatic malaria infection in Indonesian children

Abstract

Both γδ T cells and CD4⁺ T cells have been implicated in immunity to malaria, but their association with natural gain or loss of infection has not been studied before. Therefore, we followed up asymptomatic children living in an area endemic for malaria in Indonesia for 21 months. The percentage of γδ T cells was related to both current and previous infection, with higher percentages in infected than uninfected children and declining after infections resolve. Infected children also had higher levels of Th1 and Th17 cells, lower levels of CD25^Hi FOXP3⁺ regulatory T cells (Tregs), but similar levels of Th2 cells as compared to uninfected children. However, TNF, IFN-γ, and IL-17 cytokine responses to Plasmodium falciparum-infected red blood cells (PfRBCs) were similar, while IL-5 and IL-13 responses were lower in infected children. Furthermore, infected children had more phenotypically exhausted PD-1⁺ CD4⁺ T cells, more Tregs expressing TNF-RII, and higher IL-10 responses to PfRBCs, which persisted following resolution of infection. Altogether, this study demonstrates that asymptomatic malaria infection is associated with some long-lasting changes in the frequencies and immunoregulation of circulating innate and adaptive T cells, which might in part explain how pre-exposure to malaria affects responses to subsequent immunological challenges.