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Trimodal single-cell profiling reveals a novel pediatric CD8αα T cell subset and broad age-related molecular reprogramming across the T cell compartment. | LitMetric

AI Article Synopsis

  • * Results indicate that as people age, T cell subsets shift toward a more activated state, and naive CD4 T cells undergo significant genetic changes despite previously being thought resilient to aging.
  • * A new subtype of CD8αα T cells, which is lost with age and is important for quick immune responses, was identified, highlighting the complex molecular changes in T cells that may influence how the immune system functions differently

Article Abstract

Age-associated changes in the T cell compartment are well described. However, limitations of current single-modal or bimodal single-cell assays, including flow cytometry, RNA-seq (RNA sequencing) and CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), have restricted our ability to deconvolve more complex cellular and molecular changes. Here, we profile >300,000 single T cells from healthy children (aged 11-13 years) and older adults (aged 55-65 years) by using the trimodal assay TEA-seq (single-cell analysis of mRNA transcripts, surface protein epitopes and chromatin accessibility), which revealed that molecular programming of T cell subsets shifts toward a more activated basal state with age. Naive CD4 T cells, considered relatively resistant to aging, exhibited pronounced transcriptional and epigenetic reprogramming. Moreover, we discovered a novel CD8αα T cell subset lost with age that is epigenetically poised for rapid effector responses and has distinct inhibitory, costimulatory and tissue-homing properties. Together, these data reveal new insights into age-associated changes in the T cell compartment that may contribute to differential immune responses.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602854PMC
http://dx.doi.org/10.1038/s41590-023-01641-8DOI Listing

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