Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission.
Proc Natl Acad Sci U S A
; 112(44): 13645-50, 2015 Nov 03.
Article
em En
| MEDLINE
| ID: mdl-26483473
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Infecções por Citomegalovirus
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Transmissão Vertical de Doenças Infecciosas
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Troca Materno-Fetal
Limite:
Animals
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Pregnancy
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2015
Tipo de documento:
Article