Distinct activation programs in naive and memory CD8 T cells govern stemness and effector persistence of their progeny
- 1Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czechia
Abstract
Infection- and vaccination-induced memory CD8+ T cells provide protection upon subsequent exposure to cognate antigen through their increased abundance and robust per-cell responses. However, how prior antigen experience alters T-cell activation programs remains poorly understood. We longitudinally profiled gene expression in naive, central memory, and effector memory CD8+ T cells in response to cognate antigen across multiple models of acute infection. Naive T cells engaged TOX- and TCF7-centered programs and generated early stem-like central memory precursors. Their initially slow proliferation was followed by rapid expansion and the production of large numbers of short-lived effector cells. Central memory T cells rapidly triggered effector and proliferation programs while maintaining a smaller self-renewing population. Effector memory T cells expanded poorly and generated almost exclusively effector progeny. Effector progeny derived from both memory subsets survived contraction more efficiently than naive T-cell-derived progeny and established persistent effector memory populations. These data show that prior antigen experience does not simply accelerate CD8+ T-cell activation but redirects cell-intrinsic programs that shape progeny fate and persistence. These distinct programs may reflect adaptation to primary versus repeated antigen exposure and suggest that infection and vaccination history can shape the balance between stem-like memory and persistent effector populations.
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BibTeX
@misc{salyova2026distinct,
title = {{Distinct activation programs in naive and memory CD8 T cells govern stemness and effector persistence of their progeny}},
author = {E. Salyova and D. Paprckova and J. Michalik and V. Niederlova and V. Cimermanova and K. Tomicova and A. Drobek and V. Racek and A. Moudra and A. Morales Mendez and M. Krupkova and R. Sedlacek and O. Stepanek},
howpublished = {bioRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.22.740179},
url = {https://www.biorxiv.org/content/10.64898/2026.07.22.740179v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Distinct activation programs in naive and memory CD8 T cells govern stemness and effector persistence of their progeny
AU - E. Salyova
AU - D. Paprckova
AU - J. Michalik
AU - V. Niederlova
AU - V. Cimermanova
AU - K. Tomicova
AU - A. Drobek
AU - V. Racek
AU - A. Moudra
AU - A. Morales Mendez
AU - M. Krupkova
AU - R. Sedlacek
AU - O. Stepanek
PY - 2026
DA - 2026/07/22
PB - bioRxiv
DO - 10.64898/2026.07.22.740179
UR - https://www.biorxiv.org/content/10.64898/2026.07.22.740179v2
AB - Infection- and vaccination-induced memory CD8+ T cells provide protection upon subsequent exposure to cognate antigen through their increased abundance and robust per-cell responses. However, how prior antigen experience alters T-cell activation programs remains poorly understood. We longitudinally profiled gene expression in naive, central memory, and effector memory CD8+ T cells in response to cognate antigen across multiple models of acute infection. Naive T cells engaged TOX- and TCF7-centered programs and generated early stem-like central memory precursors. Their initially slow proliferation was followed by rapid expansion and the production of large numbers of short-lived effector cells. Central memory T cells rapidly triggered effector and proliferation programs while maintaining a smaller self-renewing population. Effector memory T cells expanded poorly and generated almost exclusively effector progeny. Effector progeny derived from both memory subsets survived contraction more efficiently than naive T-cell-derived progeny and established persistent effector memory populations. These data show that prior antigen experience does not simply accelerate CD8+ T-cell activation but redirects cell-intrinsic programs that shape progeny fate and persistence. These distinct programs may reflect adaptation to primary versus repeated antigen exposure and suggest that infection and vaccination history can shape the balance between stem-like memory and persistent effector populations.
ER -