Activation status of cord blood gamma delta T cells reflects in utero exposure to Plasmodium falciparum antigen.

Abstract

BACKGROUND: Placental Plasmodium falciparum infection modulates neonatal cell-mediated immune responses and is associated with increased susceptibility of infants to malaria. METHODS: By flow-cytometric analysis of maternal peripheral and cord blood samples collected at delivery, we measured and compared the activation status and proinflammatory cytokine activity of T cells from women segregated into groups according to malaria status. RESULTS: Stimulation with phorbol myristate acetate/ionomycin resulted in the highest percentages of tumor necrosis factor-alpha- and interferon-gamma-positive gamma delta T cells in peripheral blood samples and in corresponding cord blood samples from those treated for malaria during pregnancy. Cord blood samples from this group also contained significantly higher percentages of CD69(+) and CD25(+) gamma delta T cells and CD3(+) T cells, compared with samples from either the group with active placental P. falciparum infection at delivery or the group with no infection. Proinflammatory cytokine activity of cells from the group with placental P. falciparum infection at delivery was either similar to or lower than that of cells from the group with no infection. CONCLUSIONS: The findings imply that treatment of P. falciparum malaria during pregnancy leads to enhanced innate immune T cell activation and proinflammatory cytokine responses in both maternal and fetal compartments. Ongoing placental P. falciparum infection, conversely, is associated with an absence of such activity.