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Updated: Jan 5, 2026

Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells
Published on: October 19, 2021
Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling
Flavian D Brown1,2,3,4,5,6, Debattama R Sen1,2, Martin W LaFleur1,2,3,4
1Division of Medical Sciences, Harvard Medical School, Boston, MA, USA.
Abstract:
Lymph node fibroblastic reticular cells (FRCs) respond to signals from activated T cells by releasing nitric oxide, which inhibits T cell proliferation and restricts the size of the expanding T cell pool. Whether interactions with FRCs also support the function or differentiation of activated CD8+ T cells is not known. Here we report that encounters with FRCs enhanced cytokine production and remodeled chromatin accessibility in newly activated CD8+ T cells via interleukin-6. These epigenetic changes facilitated metabolic reprogramming and amplified the activity of pro-survival pathways through differential transcription factor activity. Accordingly, FRC conditioning significantly enhanced the persistence of virus-specific CD8+ T cells in vivo and augmented their differentiation into tissue-resident memory T cells. Our study demonstrates that FRCs play a role beyond restricting T cell expansion-they can also shape the fate and function of CD8+ T cells.
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