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.

疟疾仍然是全世界发病率和死亡率的重要原因，尤其是在婴儿和儿童中。一些研究报告说，暴露于子宫内的疟疾抗原会导致耐受性的发展，这可能导致生命早期对疟疾的免疫力较差。然而，尚未充分表征效应子T细胞对子宫内遇到的病原体衍生抗原（包括疟疾）的反应。在这里，我们评估了有或没有胎盘疟疾的母亲所生的乌干达婴儿的脐血T细胞的频率，表型和功能。我们发现，患有活动性胎盘疟疾的母亲所生的婴儿的胎儿记忆性CD4 ⁺ T细胞增殖效应频率升高，而CD4 ⁺和CD8 ⁺频率升高产生炎性细胞因子的T细胞。暴露于胎盘疟疾的婴儿的胎儿CD4 ⁺和CD8 ⁺ T细胞在体外对疟疾抗原表现出更大的增殖。疟疾特异性CD4 ⁺ T细胞增殖与儿童期对疟疾的前瞻性保护相关。这些数据证明胎盘疟疾与促炎性疟疾反应性胎儿T细胞的产生有关。这些发现增加了我们目前对胎儿免疫力的理解，并表明可以在子宫内产生功能性和保护性病原体特异性T细胞应答。