학술논문

In utero priming of highly functional effector T cell responses to human malaria
Document Type
article
Source
Science Translational Medicine. 10(463)
Subject
Medical Microbiology
Biomedical and Clinical Sciences
Clinical Sciences
Immunology
Perinatal Period - Conditions Originating in Perinatal Period
Prevention
Pediatric
Infectious Diseases
Rare Diseases
Vector-Borne Diseases
Conditions Affecting the Embryonic and Fetal Periods
Clinical Research
Malaria
2.1 Biological and endogenous factors
Aetiology
Infection
Inflammatory and immune system
Reproductive health and childbirth
Good Health and Well Being
Antigens
Protozoan
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Differentiation
Cell Proliferation
Cross-Priming
Cytokines
Female
Fetus
Humans
Immunologic Memory
Infant
Inflammation Mediators
Peptides
Pregnancy
T-Lymphocytes
Biological Sciences
Medical and Health Sciences
Medical biotechnology
Biomedical engineering
Language
Abstract
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.