Development of Human Cytomegalovirus—Specific T Cell Immunity during Primary Infection of Pregnant Women and Its Correlation with Virus Transmission to the Fetus

• Published in: The Journal of infectious diseases Vol. 195; no. 7; pp. 1062 - 1070
• Main Authors: Lilleri, Daniele, Fornara, Chiara, Furione, Milena, Zavattoni, Maurizio, Revello, Maria Grazia, Gerna, Guiseppe
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.04.2007; University of Chicago Press
• Subjects: Adolescent; Adult; Biological and medical sciences; Blood; Case-Control Studies; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus infections; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - transmission; Female; Fetus; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Human cytomegalovirus; Humans; Infant, Newborn; Infections; Infectious Disease Transmission, Vertical; Infectious diseases; Interferon-gamma - analysis; Interleukin-2 - analysis; Medical sciences; Microbiology; Miscellaneous; Pregnancy; Pregnancy Complications, Infectious - immunology; Statistical median; T lymphocytes; Virology; Viruses; Women; Virus; Human; Infection; Microbiology; Primary infection; Herpesviridae; T-Lymphocyte; Transmission; Female; Fetus; Betaherpesvirinae; Human cytomegalovirus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/512245

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.