In utero DNA immunization: Immunity over tolerance in fetal life

The function and plasticity of the developing immune system during embryonic life has been central to immunological thinking for half a century. A classical view is that antigen encountered during fetal life induces a state of acquired immunological tolerance. However, the ability to develop T cell immune responses during the perinatal period would be of great importance against intracellular pathogens. Recent experiments have challenged this notion and shown that neonatal tolerance can be circumvented by extrinsic immunological manipulations. Here, we used DNA immunization targeted at B lymphocytes to induce a CD4 T cell response that could be measured 2 weeks after birth. We conclude that T cell immunity can be programmed in utero by manipulating the parameters of the immune response in the fetal environment. Furthermore, our data suggest that under appropriate conditions the fetal immune system can be programmed to immunity.