Research ArticleMalaria

In utero priming of highly functional effector T cell responses to human malaria

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Science Translational Medicine  17 Oct 2018:
Vol. 10, Issue 463, eaat6176
DOI: 10.1126/scitranslmed.aat6176

Prenatal Plasmodium reactivity

Fetal immunity is generally thought to be skewed toward tolerance. Odorizzi et al. used samples from a study in Uganda to determine whether placental malaria infection modulated fetal immune responses to malaria. They stimulated cord blood cells in vitro and found that the fetal cells from cases of placental malaria were more reactive to Plasmodium antigens. Moreover, clinical follow-up revealed that this increased T cell response correlated with protection from childhood malaria. Their results demonstrate that protective immune responses in humans are able to develop even before birth. These findings not only contribute to our knowledge of human fetal immunity but also have implications for malaria control programs.


Malaria remains a significant cause of morbidity and mortality worldwide, particularly in infants and children. Some studies have reported that exposure to malaria antigens in utero results in the development of tolerance, which could contribute to poor immunity to malaria in early life. However, the effector T cell response to pathogen-derived antigens encountered in utero, including malaria, has not been well characterized. Here, we assessed the frequency, phenotype, and function of cord blood T cells from Ugandan infants born to mothers with and without placental malaria. We found that infants born to mothers with active placental malaria had elevated frequencies of proliferating effector memory fetal CD4+ T cells and higher frequencies of CD4+ and CD8+ T cells that produced inflammatory cytokines. Fetal CD4+ and CD8+ T cells from placental malaria–exposed infants exhibited greater in vitro proliferation to malaria antigens. Malaria-specific CD4+ T cell proliferation correlated with prospective protection from malaria during childhood. These data demonstrate that placental malaria is associated with the generation of proinflammatory malaria-responsive fetal T cells. These findings add to our current understanding of fetal immunity and indicate that a functional and protective pathogen-specific T cell response can be generated in utero.

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