Limited protection against early-life cytomegalovirus infection results from deficiency of cytotoxic CD8 T cells
https://www.biorxiv.org/content/10.1101/2024.07.10.602923v1
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 αβ T cells. Adoptive transfer of naïve 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.
Info
- Repository includes Data analysis and figure generation code for this paper.
- Processed filtered counts for the samples are not uploaded during making of this repository.
- Additional commands for generating objects, if missing, will be added later.
- Raw data in FASTQ format can be found with ENA accession: PRJEB70246