Biology subjects

Kaisenberg, C. v.

Publications and source records attributed to Kaisenberg, C. v..

2 recordsLinked to original sources

bioRxiv2026

Transcriptomic profiling of human γδ T cells reveals non-linear immune aging characterized by childhood transitions and relative stability in adulthood

{gamma}{delta} T cells are one of the first T cell subsets developing in early ontogeny and show various effector functions in immune homeostasis and response in the young and the old. However, their maturation trajectories from infancy to children, adults and elderly have not been systematically defined. Here, we generated a single-cell transcriptome atlas of 106,711 {gamma}{delta} T cells from 223 individuals spanning infancy to old age. Our analysis reveals that {gamma}{delta} T cell aging is non-linear, characterized by pronounced childhood transitions followed by relative stability throughout adulthood despite marked inter-individual variability. In childhood, changes from developmental and mitochondrial programs toward cytotoxicity and inflammaging were evident. This includes maturation trajectories from GZMK intermediates to GZMB+Perforin+ effectors at both RNA and protein levels. Taken together, our study delineates the aging trajectories of human {gamma}{delta} T cells, establishes {gamma}{delta} T cells as a cellular paradigm of non-linear immune aging, and provides a comprehensive resource for investigating {gamma}{delta} T cell biology across the human lifespan.

immunology↗

bioRxiv2020

A fetal wave of human type-3 γδ T cells with restricted TCR diversity persists into adulthood

Accumulating evidence suggests that the human embryonic thymus produces distinct waves of innate effector {gamma}{delta} T cells. However, it is unclear whether this process comprises a dedicated subset of IL-17-producing {gamma}{delta} T ({gamma}{delta}T17) cells, like reported in mice. Here we present a novel protocol for high-throughput paired {gamma}{delta} TCR-sequencing, which in combination with single-cell RNA-sequencing revealed a high heterogeneity of effector {gamma}{delta} T cell clusters. While immature {gamma}{delta} T cell clusters displayed mixed and diverse TCR, effector cell types in neonatal and adult blood segregated according to {gamma}{delta}TCR usage. In adult samples, mature V{delta}1+ T cells segregated into exhausted PD-1hi and active PD-1low clusters. Among V{gamma}9V{delta}2+ T cell subsets, we identified distinct PLZF-positive effector {gamma}{delta} T cell clusters with innate type-1 and type-3 T cell signatures that were already detectable in a public dataset of early embryonic thymus organogenesis. Together, this suggests that functionally distinct waves of human innate effector {gamma}{delta} T cells including CCR6+ {gamma}{delta}T17 cells develop in the early fetal thymus and persist into adulthood.

immunology↗