The data from the present study has provided evidence for antigen-specific T cell responses to A. lumbricoides antigens in utero suggested by the observation of increased frequencies of antigen-specific IFN-γ and IL-4-expressing CD4+ T cells in cord blood from newborns of A. lumbricoides-infected compared to those of non-infected mothers.
Although the data were collected during a small case-control study, we were able to show statistically significant effects between newborns of infected and non-infected mothers for the two cytokines measured. The fact that mothers were recruited from the same maternity department over a short period of 2 months, the analyses were performed blind to maternal infection status, and the newborns were balanced with respect to potential confounders, make the data more compelling. The absence of detectable anti-Ascaris
IgE in cord blood in the newborns of uninfected mothers and negative alkaline denaturation tests makes significant admixture of maternal and fetal blood unlikely. We measured CD4+ T cell responses because a previous study has shown that cytokine production by helminth antigen-stimulated cord blood lymphocytes is primarily dependent on CD4+ T cells.2
Maternal A. lumbricoides
infections may sensitize fetal immunity either by passage of parasite antigens or maternal anti-idiotype IgG antibodies across the placenta. A. lumbricoides
antigens can be detected in the peripheral blood of infected individuals7
even though adult parasites are confined to the intestinal lumen. The absence of anti-Ascaris
IgE in cord blood samples may indicate a lack of appropriate signals for IgE production by fetal B cells. The fetus is capable of producing IgE from the eleventh week of gestation.5
Previous studies have indicated that maternal schistosomiasis,2,5
and hookworm infection9
but not ascariasis10
are associated with the presence of parasite-specific IgE in cord blood. Analysis of an additional 86 cord blood plasma samples from newborns of 43 Ascaris
-infected and 43 non-infected mothers at the same Hospital failed to detect anti-Ascaris
IgE in any of the samples (authors' unpublished data). Adult filarial and schistosome parasites live in the lymphatics and venous system, respectively, and greater quantities of antigen from these parasites may reach the placental circulation compared to adult geohelminths. Similarly, greater quantities of antigen are likely to be released into the circulation by the large quantities of filarial larvae and schistosome eggs that are typically present in infected individuals compared to the larvae of A. lumbricoides
or hookworm undergoing systemic migration. For this reason, it is more likely that maternal filarial and schistosome parasites will sensitize the fetus for specific IgE. The single study that reported hookworm-specific IgE in newborns of infected mothers appeared to measure only low-titer antibodies.9
The discrepant findings between newborns of Ascaris
and hookworm-infected may be explained by parasite-specific effects, false positive serologic reactions, or the inability to detect very low titer IgE by the assay we used (detection limit of 0.35 kU/L).
Previous studies have shown that cord blood lymphocytes from newborns of helminth- infected mothers produce substantial amounts of IFN-γ8
but also IL-42
In the present study, we observed a possible Th1-skewing of the A. lumbricoides
-specific response - suggested by higher frequencies of CD4+ T cells expressing IFN-γ compared to IL-4 and the absence of anti-Ascaris
IgE - among newborns compared to their mothers. Previous studies of newborn infants of mothers with schistosomiasis showed that skin testing with parasite extracts did not induce immediate hypersensitivity responses but did induce delayed type hypersensitivity and migration inhibition responses that may suggest strong anti-helminth Th1 responses at birth.11,12
The risk of allergic disease is low in areas of the rural tropics where geohelminth infections are highly prevalent and it has been suggested that these infections may suppress allergic inflammation.1
Early exposures and infections with helminths may be important in mediating these effects and such a hypothesis is supported by the observations of early effects on the risk of allergy of maternal helminth13
and infant infections.14
It has been suggested that these suppressive effects may be mediated by IL-10,15
a cytokine not measured in the present study.
In addition to effects on allergy, sensitization of the fetus to maternal ascariasis may have other important consequences including: 1) enhanced or reduced susceptibility to childhood infections with A. lumbricoides
depending on the type of immune response generated in the newborn;4
2) increased susceptibility to other infectious diseases such as HIV3
and 3) possible effects on morbidity caused by ascariasis or other helminth infections.
The data from the present study provide evidence for specific sensitization to A. lumbricoides antigens in newborns of infected mothers. We demonstrated increases in the frequencies of CD4+ T cells expressing IFN-γ and IL-4 after in vitro stimulation with Ascaris antigens. The findings suggest that the immune modulatory effects on host immunity attributed to A. lumbricoides infection may start in utero. An understanding of how these parasites mediate such regulatory effects may have important implications for our understanding of the regulation of inflammation in childhood in the rural tropics.