Neonatal T cells unleash innate powers to combat congenital cytomegalovirus infection

Abstract

Approximately 1 in 200 newborns worldwide are affected by congenital cytomegalovirus (CMV). Most of these cases are asymptomatic due to successful control of the infection by the newborn's immune system. In this issue of the JCI, Semmes et al. characterized the cellular immune response in cord blood of neonates with CMV infection. The authors found that conventional T cells with NK-like features expanded during congenital CMV infection. To exert their antiviral function, these cells relied on Fc receptors, recognizing virus-infected cells bound by IgG. Thereby, the fetal and maternal immune system can optimally cooperate to control CMV infection: maternal IgG crossing the placenta opsonizes virus-infected cells subsequently lysed by neonatal NK-like T cells. This finding suggests that innate-like programming of conventional T cells may have evolved to combat congenital CMV infection, offering insights that could inform the development of future therapies.

Figure 1. Fetomaternal immune systems collaborate in the control of congenital CMV infection.

During congenital CMV infection, maternal IgG against CMV crosses the placenta. Conventional CD8⁺ T cells upregulate FcγRIII and NKG2C, transdifferentiating into FcRT cells. Maternal IgGs elicit antibody-dependent cellular cytotoxicity (ADCC) by FcRT cells and NK cells. NK cells also target and lyse virus-infected cells directly via NKG2C-activating receptors.