Early life programming of post-natal health 3159

Abstract Description Vertebrate animals undergo layered hematopoiesis during development, with certain immune cells generated exclusively during the prenatal period. While bone marrow replenishes the immune repertoire in adulthood, some immune cells are restricted to early life. Environmental stress during early lineage specification can permanently alter the development of these cells. We hypothesize that immune cells restricted to early life are vulnerable to pathological programming by the maternal environment, leading to long-term health impacts due to a “missed developmental window.” In a model of gestational influenza B virus (IBV) infection and cross-fostering, neonates from IBV-infected dams (mIBV) had lower birth weights and altered γδT cell development in the thymus when compared to age-matched controls (mPBS). Although no vertical transmission was detected, adult male mIBV offspring fostered to control dams were more susceptible to lung fibrosis, indicating long-lasting effects of gestational stress. Interestingly, γδT cell differences in mIBV and mPBS neonatal thymus amplified in the lungs of adult offspring. Preliminary data suggest that neonatal mIBV γδT cells are impaired in rescuing weight loss in TCRδ-/- mice with lung fibrosis. Adoptively transferred mIBV γδT cells showed reduced IL-17 production and increased CD27 expression compared to controls. These findings support the hypothesis that transient maternal insults to fetal immune cells can negatively affect long-term health. Funding Sources CRI Irvington Postdoctoral Fellowship Bernard Levine Fellowship Topic Categories Hematopoiesis and Immune System Development (HEM)