Studies have clearly established the presence of T and B cell responses by the human fetus to maternal parasitic infections 
. Animal models suggest that exposure to parasites in utero may be either beneficial (by accelerating the development of protective antibodies and cellular immune responses) or detrimental (by impairing the acquisition of a protective immune response and inducing immune tolerance) 
Immune tolerance may be due to clonal deletion of specific cell subsets, which leads to loss of antigen-reactive cells in utero and subsequent lack of recall response during antigen exposure later in infancy. Another possible tolerance mechanism is clonal anergy, which results from a lack of adequate costimulation by antigen-presenting cells to CD4+ cells. Finally, tolerance may be due to the de novo generation of populations of immunoregulatory cells. Prenatal exposure to malaria, schistosomiasis, and filariasis may lead to the acquisition of a subset of immunoregulatory CD4+ T cells. A distinct population of CD4+ regulatory-1 cells (Tr1) has been shown to be able to arise from CD34+ cells in the neonate 
in response to IL-10 and IFN-α 
. Specifically, IL-10 has been proposed to be responsible for modulating subsequent immune responses during subsequent exposure to new, unrelated antigens. Tr1 cells are antigen-specific CD4+ cells that are distinct from Th1 and Th2 cells in that they produce significant amounts of IL-10, variable IFN-γ, TGF-β, and IL-5, but little or no IL-2 and no IL-4. The CD4+CD25+ T cells represent another population of regulatory T cells whose development is partially mediated by IL-10 and TGF-β 
. As with chronic helminth infections, exposure to maternal malaria leads to the generation of significant levels of malaria blood stage antigen-driven IL-10 in cord blood and infant lymphocytes. Presumably, this immunomodulation may benefit the human host by limiting inflammation caused by chronic parasite infections in early childhood and later adolescence. However, the concomitant downside is a reduced ability to respond to acute bacterial and viral infections and to vaccination.
In humans, “tolerance” (manifested by the generation of immunoregulatory populations of lymphocytes by prenatal antigenic exposure) is likely to contribute to the long-term persistence of many intravascular parasitic infections 
. In our studies, tolerance is defined as an altered or suppressed immune response to parasite antigens during infancy or childhood in the progeny of women infected during pregnancy. Maternal infection with lymphatic filariasis, schistosomiasis, and the protozoan parasites Trypanosoma cruzi
and T. gondii
have been shown to enhance the offspring's susceptibility to subsequent infection, and this phenomenon is associated with impaired or altered fetal immune response to parasite antigens. Children born to filarial-infected mothers, for example, have depressed cytokine responses in T cells and lymphocyte proliferation by peripheral blood mononuclear cells to filarial antigens compared to offspring from uninfected mothers. They are also significantly more likely to acquire filarial infection in the first 5 years of life and continue to show altered responses to parasite antigens years after birth 
Not all in utero exposure to maternal helminth infections results in tolerance. Instead, for some newborns, prenatal parasite exposure results in a constant state of antiparasite immune activation that is characterized by a Th2-dominant cytokine profile, high IgE levels, and eosinophilia. Such an immune profile also may have an adverse impact on the efficacy of vaccines by limiting Th1 pathways of immune response to vaccination. By altering the immunologic balance between Th1 and Th2 pathways, chronic parasitic infections appear to alter the immunologic milieu and would also likely impair or suppress the “normal” responses to vaccines that have been described in parasite-free, developed countries.