Human Cytomegalovirus-Specific Memory CD4+ T-Cell Response and Its Correlation With Virus Transmission to the Fetus in Pregnant Women With Primary Infection

Abstract

Background: Primary human cytomegalovirus (HCMV) infection during pregnancy is the major cause of congenital viral sequelae. The HCMV-specific T-cell response may have a role in the prevention of virus transmission to the fetus.

Methods: HCMV-specific memory T cells were investigated in the second month after primary infection onset in 44 pregnant women (15 transmitting the infection to the fetus) and 8 pregnant women with remote infection. Peripheral blood mononuclear cells were stimulated for 12 days with peptide pools of HCMV proteins IE-1, IE-2, and pp65, and subsequently restimulated for 24 hours with the same peptide pools in a cultured enzyme-linked immunospot (ELISPOT) assay.

Results: In pregnant women with primary infection, the cultured ELISPOT assay detected a higher T-cell response to pp65 than to IE-1 or IE-2, whereas in remote infection pp65-, IE-1-, and IE-2-specific T cells were detected at comparable levels. During primary infection, the cultured ELISPOT response was mainly mediated by CD4+ T cells, and was lower than in remote infection. Strikingly, the cultured ELISPOT response to pp65 (but not to IE-1 or IE-2) was significantly higher in nontransmitting mothers. To detect other factors potentially associated with nontransmission, different serological parameters were analyzed. Only immunoglobulin G avidity index was higher in nontransmitting mothers, who showed also a lower DNAemia level. These 2 parameters remained associated with congenital infection in multivariate analysis.

Conclusions: Determination of HCMV-specific T cells by cultured ELISPOT, in pregnant women with primary HCMV infection, in association with avidity index and DNAemia may help to assess the risk of HCMV fetal transmission.

Keywords: cell-mediated response; congenital infection; human cytomegalovirus; pregnancy.