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Updated: Aug 15, 2026

In Vitro Resident Memory CD8 T Cell Differentiation Using Epithelial Organoid-T Cell Co-culture System
Published on: February 3, 2026
Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin
Andrew M Intlekofer1, Naofumi Takemoto, E John Wherry
1Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Abstract:
Two seemingly unrelated hallmarks of memory CD8(+) T cells are cytokine-driven proliferative renewal after pathogen clearance and a latent effector program in anticipation of rechallenge. Memory CD8(+) T cells and natural killer cells share cytotoxic potential and dependence on the growth factor interleukin 15. We now show that mice with compound mutations of the genes encoding the transcription factors T-bet and eomesodermin were nearly devoid of several lineages dependent on interleukin 15, including memory CD8(+) T cells and mature natural killer cells, and that their cells had defective cytotoxic effector programming. Moreover, T-bet and eomesodermin were responsible for inducing enhanced expression of CD122, the receptor specifying interleukin 15 responsiveness. Therefore, these key transcription factors link the long-term renewal of memory CD8(+) T cells to their characteristic effector potency.
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