Limited protection against early-life cytomegalovirus infection results from deficiency of cytotoxic CD8T cells
Fonseca Brito, L.; Ostermann, E.; Perez, A.; Toedter, S.; Virdi, S.; Indenbirken, D.; Glau, L.; Gieras, A.; Brixel, R.; Arens, R.; Grundhoff, A.; Arck, P.; Diemert, A.; Tolosa, E.; Brune, W.; Stahl, F. R.
Show abstract
Differential antiviral T cell immunity in early life impacts the clinical outcome of Cytomegalovirus (CMV) infection, but the underlying mechanisms are not well understood. Here, we found delayed enrichment of early-life murine CMV-specific CD8 T cells due to a general deficiency of {beta} T cells. Adoptive transfer of naive adult T cells into neonates did not protect due to a blockade of CD8 but not of CD4 effector T cell differentiation. Early-life deficiency of critical signal 3 cytokines during T cell priming resulted in the appearance of 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 defective CD8 T cell immunity as an important factor explaining the higher risk for CMV disease in the early-life phase.
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