Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission. Academic Article uri icon

Overview

abstract

  • Elucidation of maternal immune correlates of protection against congenital cytomegalovirus (CMV) is necessary to inform future vaccine design. Here, we present a novel rhesus macaque model of placental rhesus CMV (rhCMV) transmission and use it to dissect determinants of protection against congenital transmission following primary maternal rhCMV infection. In this model, asymptomatic intrauterine infection was observed following i.v. rhCMV inoculation during the early second trimester in two of three rhCMV-seronegative pregnant females. In contrast, fetal loss or infant CMV-associated sequelae occurred in four rhCMV-seronegative pregnant macaques that were CD4(+) T-cell depleted at the time of inoculation. Animals that received the CD4(+) T-cell-depleting antibody also exhibited higher plasma and amniotic fluid viral loads, dampened virus-specific CD8(+) T-cell responses, and delayed production of autologous neutralizing antibodies compared with immunocompetent monkeys. Thus, maternal CD4(+) T-cell immunity during primary rhCMV infection is important for controlling maternal viremia and inducing protective immune responses that prevent severe CMV-associated fetal disease.

publication date

  • October 19, 2015

Research

keywords

  • CD4-Positive T-Lymphocytes
  • Cytomegalovirus Infections
  • Infectious Disease Transmission, Vertical
  • Maternal-Fetal Exchange

Identity

PubMed Central ID

  • PMC4640765

Scopus Document Identifier

  • 84946601394

Digital Object Identifier (DOI)

  • 10.1073/pnas.1511526112

PubMed ID

  • 26483473

Additional Document Info

volume

  • 112

issue

  • 44