Early-life cytomegalovirus infection susceptibility results from generation of non-cytotoxic antiviral CD8 T cells

Differential antiviral immunity in early life impacts the clinical outcome of Cytomegalovirus (CMV) infection but the CMV-specific cytotoxic T lymphocyte (CTL) effector function is not well understood in neonates. Here, we found delayed enrichment of murine CMV-specific CD8 T cells in neonates due to a general deficiency of aßT cells in their first days of life. Adoptive transfer of adult T cells into neonates led to a selective block in effector T cell differentiation for CD8 but not for CD4 T cells. Deficiency of critical signal 3 cytokines during respiratory tract T cell priming resulted in non-cytotoxic CD8 effector T cells whereas the effector phase of adult-primed T cells was not disrupted in neonates. Accordingly, we found an overall low number of antiviral human CD8 T cells in newborns with congenital CMV. Together, this study suggests a defective CD8 T cell response as an important factor explaining the increased virus susceptibility in the early-life phase.