Cytomegalovirus in the Neonate: Immune Correlates of Infection and Protection

Table 2

Summary of adaptive immune responses and their proposed role in control of or susceptibility to congenital CMV infection.

Adaptive immunity and susceptibility/protection in congenital CMV infection
Immune effector	Maternal/placental/fetal compartment	Proposed effect on CMV transmission/disease
CD4+ T cells	Maternal compartment; Fetal/neonatal compartment	(i) Delayed development of CD4+ T-cell lymphoproliferative response correlates with maternal-fetal transmission; (ii) Defective CD4+ immunity; diminished IF-𝛾 and IL-2 production in fetal and early childhood infection; (iii) Defective fetal CD4+ response may contribute to congenital CMV infection and disease
T-regs	Maternal compartment	(i) Treg expansion: normal response to pregnancy; (ii) ↓ Tregs: correlates with protection against CMV disease in transplant recipients; (iii) Relevance to congenital CMV unknown
CD8+ T cells	Maternal compartment; Fetal/neonatal compartment	(i) CD8+ response to infection appears unaltered in pregnancy; (ii) Fetal CD8+ response to CMV antigens noted as early as week 22 gestation; (iii) Exhibit cytolytic properties and elucidate IF-𝛾; (iv) Some studies raise questions about functionality?
Gammadelta T cells	Neonatal compartment	(i) Fetal gammadelta T cells differentiate and expand in setting of congenital CMV infection; (ii) Produce IF-𝛾 and other cytokines; (iii) Role in protection of fetus, control of virus not clear
Antibody	Maternal compartment; Placental compartment; Fetal compartment	(i) Variability in maternal antibody response based on viral strain variation, possibly TLR polymorphisms; (ii) Expression of neonatal Fc receptor may paradoxically promote transcytosis of CMV particles across syncytiotrophoblast by low-avidity antibody; (iii) High avidity antibody may neutralize CMV at placental interface; (iv) Transplacental transfer of therapeutic neutralizing antibody may improve outcome of infected fetus