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*
Division of Geographic Medicine, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Cleveland, OH 44106;
Division of Vector Borne Diseases, Ministry of Health, Nairobi, Kenya;
Kenya Medical Research Institute, Nairobi, Kenya; and
§
Veteran’s Affairs Medical Center, Cleveland, OH 44106
Infants and children are routinely vaccinated with bacillus
Calmette-Guérin (BCG) in areas of the world where worm infections
are common. Because maternal helminth infection during pregnancy can
sensitize the developing fetus, we studied whether this prenatal
immunity persists in childhood and modifies 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-
in response to
mycobacterial purified protein derivative than children of
helminth-infected mothers (p < 0.01). This
relationship was restricted to purified protein derivative because
maternal infection status did not correlate with filarial Ag-driven
IL-2, IFN-, IL-4, or IL-5 responses by children. Prospective studies
initiated at birth showed that helminth-specific T cell 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- production evaluated 10–14 mo after
BCG vaccination was 26-fold higher for infants who were not sensitized
to filariae or schistosomes in utero relative to subjects who
experienced prenatal sensitization (p < 0.01).
These data indicate 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- responses associated with protection against
mycobacterial infection.
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