Preferential development of Th17 cells in offspring of immunostimulated pregnant mice

Abstract

Pregnant mice were stimulated at day 12 of gestation with the nucleotide poly(I:C). At 24h after stimulation, serum levels of maternal cytokines were measured, and at postnatal ages 2 and 3 weeks, offspring were analyzed for T helper (Th) cell subsets. Lymphocytes from offspring of poly(I:C)-injected (vs. control PBS-injected) pregnant dams preferentially developed into T helper 17 (Th17) cells upon in vitro activation. This occurred in offspring of pregnant dams who exhibited an immunological "memory" phenotype, but not in offspring of immunologically "naïve" dams. Preferential development of Th17 cells in these offspring may be facilitated by the higher levels of pro-inflammatory cytokines such as IL-6, found in immune vs. naïve pregnant dams. Murine immune stimulation during pregnancy is frequently used to model human neurological disorders, such as autism and schizophrenia. However, immune stimulation of women during pregnancy occurs in the context of an immunological "memory" phenotype, resulting from previous immunizations and/or natural exposure to micro-organisms and other antigens. Therefore, use of previously immunized female mice with a similar immunological memory phenotype to study maternal immune stimulation during pregnancy presents a more biologically relevant experimental strategy to investigate developmental, behavioral, and immunological sequelae of offspring in such rodent models.