Phenotypic and functional heterogeneity of naïve CD8+ T cells in human peripheral blood during aging

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Abstract
Naïve CD8+ T cells are key players of adaptive immunity, but their heterogeneity and age-related changes are not fully understood. This study aimed to compare naïve CD8+ T cell subsets defined by different combinations of markers, namely NCCR7 (CD45RA+CCR7+), NCD28 (CD45RA+CD28+), NCD27 (CD45RA+CD27+), and phenotypically most "true-naïve"-like, NTN (CD45RA+CCR7+CD28+CD27+CD57-). Peripheral blood was harvested from donors of various ages and the phenotype of the four subsets of naïve CD8+ T cells was analyzed. NCD27 and NTN cells showed similar phenotypes with low expression of differentiation markers, pro-inflammatory cytokines, and effector molecules. Furthermore, they exhibited optimal mitochondrial fitness, low senescence markers, reduced apoptosis, and high proliferation potential. Hierarchical clustering identified cluster 1 including NCD27 and NTN, with lower expression of differentiation markers and pro-inflammatory molecules, and cluster 2, including NCCR7 and NCD28 cells, in which these parameters were more expressed. Age-related changes were observed in all subsets, although they were less pronounced for the NCD27 and NTN subsets. Taken together, this study demonstrates significant heterogeneity among naïve CD8+ T cell subsets, with NTN cells representing the most bona fide naïve phenotype and NCD27 showing a partially similar phenotype. These findings significantly enhance our understanding of naïve CD8+ T cell biology and function.
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Authors Weinberger, Birgit
Journal Frontiers in surgery
Year Year not found
DOI
10.3389/fragi.2026.1765665
URL
https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2026.1765665/full
Keywords Keywords not found

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