Age influences CMV-specific NK and CD8 T cell memory fates

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B169
Abstract ID: 5503

Presenting Author:
Isaac Jensen , Post Doc at Columbia Univ. Irving Med. Ctr.

Abstract:

Cytomegalovirus (CMV), a prevalent persistent infection often unnoticed in healthy adults, is the most common congenital infection of neonates/ infants. NK cells and CD8 T cells control CMV via cytolysis of infected cells; 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. Infant mice had higher viral burden and delayed viral clearance in multiple tissues.  T cell depletion enhanced infant MCMV-induced morbidity; yet, co-adoptive transfer of adult and infant OT-I CD8 T cells  followed by MCMV-OVA infection revealed phenotypic and transcriptional limits in infant T cell capacity to form memory precursors and subsequent memory. This impairment was age-dependent, co-transfer of OT-I cells from sequentially aged mice had increasing memory formation, overall infant CD8 T cells are effector biased with limited memory potential. To reconcile how infants bridge this gap in T cell immunity we interrogated NK cell responses. Unlike adult mice, infant Ly49H+ (MCMV-specific) NK cells potently responded to infection, adopting an effector-memory  (KLRG1+CD62L+) phenotype. Notably, loss of memory NK cells with age coincided with the increasing OT-I memory potential. Our data suggest discrete roles for NK cells and CD8 T cells in MCMV infection during infancy with NK cells as key responders prior to T cell ability to acquire memory.