Dataset Information

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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE286266 | GEO | 2026/04/14

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Reconstitution of cytomegalovirus (CMV)-specific immunity following transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Due to the persistence of CMV, most CMV-specific CD8+ T cells become terminally differentiated effector cells (TEFF). However, a minor subset retains a memory phenotype (TM). Interestingly, recent studies suggest that CMV-specific CD8+ T cells with different phenotypes may have different abilities to reconstitute sustained immunity following transfer. The immunology of human CMV (HCMV) infections is reflected in the mouse model of MCMV infection. We found that HCMV- and MCMV-specific T cells displayed shared genetic programs, validating the MCMV model for studies of CMV-specific T cells in vivo. After transfer, the proliferative capacity of MCMV-specific TM cells was vastly superior to TEFF cells. Strikingly, TM cells expanded and established sustained and diverse T cell populations even after multiple challenges. Although both TEFF and TM cells could protect Rag-/- mice, only TM cells could consistently survive after transfer into immune replete, latently infected recipients and respond if recipient immunity was lost. These data show that CMV-specific TM cells retain memory function during persistent infection and can re-establish CMV immunity when necessary. C57BL/6 mice were infected intraperitoneally (i.p.) with MCMV strain MW97.01 between 6-16 weeks of age. Splenocytes were isolated from chronically-infected mice and co-stained with three PE-conjugated tetramers loaded with the antigenic peptides from M38, m139 and IE3, all of which promote memory inflation. Cells were then stained with fluorescently conjugated antibodies and sorted on a MoFlo cell sorter. Naïve CD8+ cells were identified as CD44lo. MCMV-specific T cells were identified as CD8+, CD44hi and tetramer binding and then further segregated into memory and effector cells subsets by their expression of KLRG1 and CD127.

Dataset Information

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

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets