The conditions and mechanisms of congenital transmission of Trypanosoma cruzi remain largely unknown. In the present study, we compared the parasitic loads and the immune responses of pregnant T. cruzi-infected women who transmitted parasites to their fetus ("M+B+ mothers") with those of such women who did not transmit parasites to their fetus ("M+B- mothers"). M+B+ mothers had a higher frequency of positive results of hemoculture for T. cruzi than did M+B- mothers, in association with depressed production of parasite-specific interferon- gamma by blood cells that persisted after delivery. In contrast, the production of interleukin (IL)-2, IL-4, and IL-10 and transforming growth factor- beta 1 was similar between both groups of infected mothers, after stimulation with T. cruzi lysate. Flow cytometric analysis showed that T cells and monocytes of M+B+ mothers were less activated than were those of M+B- mothers. Altogether, these results indicate that congenital transmission of T. cruzi is associated with high parasitic loads and peripheral deficient immunological responses in mothers.

Fetal/neonatal immune responses generally are considered to be immature and weaker than that of adults. We have studied the cord-blood T cells of newborns congenitally infected with Trypanosoma cruzi, the protozoan agent of Chagas disease. Our data demonstrate a predominant activation of CD8 T cells expressing activation markers and armed to mediate effector functions. The analysis of the T-cell receptor beta chain variable repertoire shows the oligoclonal expansion of these T lymphocytes, indicating that activation was driven by parasite antigens. Indeed, we have detected parasite-specific CD8 T cells secreting interferon-γ after coincubation with live T cruzi. This response is enhanced in the presence of recombinant interleukin-15, which limits the T-cell spontaneous apoptosis. These findings point out that the fetal immune system is more competent than previously appreciated, since fetuses exposed to live pathogens are able to develop an adultlike immune CD8 T-cell response.