Age influences CMV-specific NK and CD8 T cell memory fates(OT-Is)

Cytomegalovirus (CMV) infection is ubiquitous; though often unnoticed in healthy adults it is a leading cause of neurodisability in neonates/ infants. NK and CD8 T cell cytolysis control CMV; yet their coordinate response to CMV remains uncharacterized, particularly in infants. We interrogated how NK and CD8 T cell responses differed between adults and infants in a murine CMV (MCMV) infection model. NK and CD8 T cells both limited infant MCMV infection morbidity. Notably, adult and infant NK cells effectuate discrete responses to MCMV infection with the latter preferentially forming memory associated with transcriptional distinctions prior to infection. Adoptive transfer studies further revealed that infant T cells are effector-biased but acquire the capacity to form memory in an age-dependent manner. Infant T cells' restricted ability to form memory was associated with a unique transcriptional state before and after infection. Further, acquisition of T cell memory capacity coincided with an age-dependent waning in the induction of adaptive NK cells. Our data suggests non-redundant roles for NK and CD8 T cells in MCMV infection during infancy, as NK cells compensate for the limited establishment of memory T cell subsets.