Abstract
BackgroundImmunity that limits malarial disease is acquired over time, but adults living in endemic areas continue to become infected and can require treatment for clinical illness. Gamma delta (γδ) T cells, particularly the Vδ2+ subset, have been associated with development of clinical malaria in children. In this study, the dynamics of total γδ T cells, Vδ2+ and Vδ2− T cells were measured during a malaria transmission season in Malian adults.MethodsThis study explored γδ T cell dynamics and Plasmodium falciparum infection outcomes over the course of the malaria transmission season in Malian adults enrolled in the placebo arm of a double-blind randomized vaccine trial. All volunteers were treated with anti-malarial drugs prior to the start of the transmission season and blood smears were assessed for P. falciparum infection every 2 weeks from July 2014 to January 2015. The study participants were stratified as either asymptomatic infections or clinical malaria cases. Vδ2+ and Vδ2− γδ T cell frequencies and activation (as measured by CD38 expression) were measured in all study participants at baseline and then every 2 months using a whole blood flow cytometry assay.ResultsForty of the forty-three subjects became infected with P. falciparum and, of those, 21 individuals were diagnosed with clinical malaria at least once during the season. The γδ T cell percentage and activation increased over the duration of the transmission season. Both the Vδ2+ and Vδ2− γδ T cells were activated by P. falciparum infection.Conclusionγδ T cells increased during a malaria transmission season and this expansion was noted in both the Vδ2+ and Vδ2− γδ T cells. However, neither expansion or activation of either γδ T cell subsets discriminated study participants that had asymptomatic infections from those that had clinical malaria cases.
Highlights
Immunity that limits malarial disease is acquired over time, but adults living in endemic areas continue to become infected and can require treatment for clinical illness
Forty-four subjects that were enrolled in the placebo arm of the PfSPZ Vaccine trial in Mali were used for the analysis of γδ T cells across the malaria transmission season in 2014
A total of 28 clinical malaria cases were recorded in 21 unique individuals during the transmission season
Summary
Immunity that limits malarial disease is acquired over time, but adults living in endemic areas continue to become infected and can require treatment for clinical illness. Gamma delta (γδ) T cells, the Vδ2+ subset, have been associated with development of clinical malaria in children. There is evidence for clinical immunity against malaria as evidenced by reduced clinical cases and greater proportions of asymptomatic infections in older children and adults [4]. Development of clinical immunity has been associated with blunted Th1 immune responses, and increases in immunoregulatory mechanism, such as T regulatory cells and IL-10 production from CD4 T cells [5,6,7]. Reduced responses of gamma delta (γδ) T cell responses to P. falciparum infections
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