Helminth- and bacillus Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis

Infants and children are routinely vaccinated with bacillus Calmette-Guerin (BCG) in areas of the world where worm infections are common. Because mate rnal helminth infection during pregnancy can sensitize the developing fetus , we studied whether this prenatal immunity persists in childhood and modif ies the immune response to BCG, Children and newborns living in rural Kenya , where BCG is administered at birth and filariasis and schistosomiasis are endemic, were examined, T cells from 2- to 10-year-old children of mothers without filariasis or schistosomiasis produced 10-fold more IFN-gamma in r esponse to mycobacterial purified protein derivative than children of helmi nth-infected mothers (p < 0.01). This relationship was restricted to purifi ed protein derivative because maternal infection status did not correlate w ith filarial Ag-driven IL-2, IFN-gamma, IL-4, or IL-5 responses by children . Prospective studies initiated at birth showed that helminth-specific T ce ll immunity acquired in utero is maintained until at least 10-14 mo of age in the absence of infection with either Wuchereria bancrofti or Schistosoma haematobium. Purified protein derivative-driven T cell IFN-gamma productio n evaluated 10-14 mo after BCG vaccination was 26-fold higher for infants w ho were not sensitized to filariae or schistosomes in utero relative to sub jects who experienced prenatal sensitization (p < 0.01). These data indicat e that helminth-specific immune responses acquired during gestation persist into childhood and that this prenatal sensitization biases T cell immunity induced by BCG vaccination away from type 1 IFN-gamma responses associated with protection against mycobacterial infection.