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.