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bioRxiv · 10.1101/2024.07.10.602923

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.
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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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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.. 2024-07-16. Limited protection against early-life cytomegalovirus infection results from deficiency of cytotoxic CD8T cells. https://doi.org/10.1101/2024.07.10.602923

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