Development of human cytomegalovirus-specific T cell immunity during primary infection of pregnant women and its correlation with virus transmission to the fetus

Abstract

Objective. We sought to study the development of human cytomegalovirus (HCMV)-specific T cell-mediated immune responses during primary HCMV infection in pregnancy. Methods. The HCMV-specific lymphoproliferative response (LPR) and intracellular cytokine (interferon [IFN]-γ and interleukin [IL]-2) production were investigated during the first year after primary infection in 49 pregnant women and 9 nonpregnant control subjects. An HCMV-specific CD4 + and CD8+ T cell LPR was detected by the 5,6-carboxyfluorescein diacetate succinimidyl ester dilution method, and a cell-division index was calculated. Results. The CD4+ T cell LPR developed slightly earlier than the CD8+ T cell LPR. However, CDI values for both T cell subpopulations were lower than those of seropositive control subjects in both pregnant and nonpregnant individuals. During the first month after infection, IFN-γ-producing CD4+ and CD8+ T cells were consistently observed, whereas IL-2-producing T cells were very rarely detected in blood. A correlation between the development of HCMV-specific LPR and virus clearance from blood was observed. A significantly delayed development of the CD4+ T cell LPR was observed in infected mothers who transmitted virus to the fetus, compared with those who did not. Conclusions. The development of adaptive T cell immunity after primary HCMV infection appears to be a complex and slow process until a memory T cell response develops. The T cell immune response appears to influence vertical HCMV transmission. © 2007 by the Infectious Diseases Society of America. All rights reserved.