Comparison of CD8+ T Cell Responses to Cytomegalovirus between Human Fetuses and Their Transmitter Mothers

Background. The mechanisms responsible for the increased susceptibility of fetuses to cytomegalovirus (CMV) were studied by comparing CD8 + T cell responses to the virus in susceptible fetuses to those in their comparatively more resistant mothers. Methods. Included in the study were 16 transmitter mothers who underwent seroconversion during the first trimester of pregnancy as well as their fetuses, who were positive for CMV in amniotic fluid by polymerase chain reaction at 17-19 weeks of gestation. Fetal and maternal blood samples were collected between the 22nd and 39th week of gestation. Cytotoxic T lymphocytes (CTLs) that had activated (HLA-DR + ), effector/memory (CD28-), and memory (CD18 high ) phenotypes; that stained with the HLA-A2/pp65 or the HLA-B7/pp65 multimer; and that secreted interferon (IFN)-γ were enumerated by flow cytometry. Viral loads were determined simultaneously. Results. The results showed (1) similar levels of activated, effector/memory, and memory CTLs in fetuses and mothers but a smaller pp65-specific CTL pool in fetuses (median, 0.015% vs. 0.99%; P =.003); (2) similar percentages of CTLs secreting IFN-γ after stimulation with ionomycin/phorbol myristate acetate in fetuses and mothers but lower percentages of CTLs secreting IFN-γ after stimulation with a CD3 monoclonal antibody in fetuses (median, 1% vs. 14%; P =.01); and (3) higher viral loads (mean, 17,290 vs. <250 genome equivalents/ mL) in fetuses. Conclusion. Impaired viral clearance might be related to a defective expansion of the pp65-specific CTL pool and/or to the immaturity of IFN-γ-secreting cells in fetuses.