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Updated: Jun 1, 2025

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
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Published on: August 13, 2013

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Metabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon

Jessica Filoni1, Arianna Ferrari1, Tatiana Jofra1

  • 1San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele Milan, Milan, Italy.

Communications Biology
|January 21, 2025
PubMed

Tregs for adoptive therapy are traditionally expanded ex vivo using high doses of IL-2. However, the final Treg product has limited survival once infused in patients, potentially affecting therapeutic effectiveness. Here, we tested a novel expansion protocol in which highly purified naïve Tregs were expanded with a combination of IL-7 and IL-15, in the absence of IL-2. The final Treg product was enriched with cells displaying an immature CD45RA+CD62L+CD95+ phenotype, reminiscent of conventional memory stem T cells. The combination of IL-7 and IL-15 confers Tregs a glycolytic metabolism and improved metabolic fitness, characterized by an increased capacity to adapt metabolism according to glucose and oxygen availability. Tregs expanded with IL-7 and IL-15 showed longer persistence and an improved capacity to control xeno-GvHD in NSG mice. This work suggests that metabolic reprogramming induced by IL-7 and IL-15 provides better Treg performance for adoptive therapy.

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