Reduced Cord Blood Immune Effector‐Cell Responsiveness Mediated by CD4⁺Cells Induced in Utero as a Consequence of PlacentalPlasmodium falciparumInfection

Abstract

To determine mechanisms of neonatal parasite antigen (Ag)-specific immune suppression associated with placental Plasmodium falciparum infection, we isolated cord blood mononuclear cells (CBMCs) from Gabonese neonates born to mothers with differing histories of P. falciparum infection and performed ex vivo and in vitro studies to evaluate immune regulatory activity. We found increased ex vivo percentages of CD4(+)CD25(hi) and CD4(+)CD25(+)CTLA-4(+) cells and increased interleukin (IL)-10 responses to parasite Ag in vitro in CBMCs from neonates born to mothers with placental P. falciparum infection at delivery. Depleting CBMCs of CD4(+)CD25(+) cells before cell culture led to the abrogation of parasite Ag-specific IL-10 responses, to enhanced interferon- gamma responses, and to enhanced expression of CD25 on CD8(+) T cells and of major histocompatibility complex class I and II on monocytes. These data demonstrate that parasite Ag-specific CD4(+) regulatory cells are generated in utero as a consequence of placental P. falciparum infection.

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth

“…Our findings would support this hypothesis. We found no effect of PM on ex vivo CD4 be increased by PM [24], whereas another Gambian study found no effect of PM on ex vivo CD4 1 CD25 1 T cells [21].…”

“…hi or CD4 1 CD25 1 T cells leads to decreased parasite Ag-specific IL-10 responses and enhanced IFN-g reactivity [21,24]. The latter study demonstrated that the CD4 1 CD25 1 cells express higher levels of FOXP3 by reverse transcription PCR than their CD4 1 CD25 counterparts [21].…”

Prenatal Malaria Immune Experience Affects Acquisition of Plasmodium falciparum Merozoite Surface Protein-1 Invasion Inhibitory Antibodies during Infancy

“…of T cells of newborns born to mothers with malaria and neonatal pups of mice infected with Plasmodium yoelii demonstrate that immunoregulatory lymphocytes of newborns are capable of suppressing malaria Ag-driven T cell responses or inducing T cell anergy (29,32,33). Taken together with the demonstration of immune tolerance to filarial parasites by a mechanism of prenatal exposure in the context of maternal infection during gestation (34,35), these findings suggest that intravascular pathogens that chronically infect women during their childbearing years may result in de facto immune tolerance when infants and children are challenged with natural infection later in life.…”

Iron Homeostasis in Mother and Child during Placental Malaria Infection

“…Archived samples from a malaria in pregnancy study, carried out in an area of Gabon characterized by stable meso-to hyperendemic malaria transmission, were used for this study. 17 Paired maternal and umbilical cord-blood samples were obtained at time of parturition from pregnant women attending the Albert Schweitzer Hospital in Lambarene, Gabon from July 2000 to February 2004. Medical records of the mothers were examined to determine whether malaria episodes were detected and appropriately treated during pregnancy.…”