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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Odorizzi, PM; Jagannathan, P; McIntyre, TI; Budker, R; Prahl, M; Auma, A; Burt, TD; Nankya, F; Nalubega, M; Sikyomu, E; Musinguzi, K; Naluwu, K; Kakuru, A; Dorsey, G; Kamya, MR; Feeney, ME

Published Date

  • October 17, 2018

Published In

Volume / Issue

  • 10 / 463

PubMed ID

  • 30333241

Pubmed Central ID

  • PMC6321770

Electronic International Standard Serial Number (EISSN)

  • 1946-6242

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.aat6176

Language

  • eng

Conference Location

  • United States