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IL-7 improves the fitness of regulatory T cells for adoptive transfer
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  • Ilaria Cosorich,
  • Jessica Filoni,
  • Carla Di Dedda,
  • Arianna Ferrari,
  • Lorenzo Piemonti,
  • Paolo Monti
Ilaria Cosorich
IRCCS Ospedale San Raffaele
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Jessica Filoni
IRCCS Ospedale San Raffaele
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Carla Di Dedda
IRCCS Ospedale San Raffaele
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Arianna Ferrari
IRCCS Ospedale San Raffaele
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Lorenzo Piemonti
IRCCS Ospedale San Raffaele
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Paolo Monti
IRCCS Ospedale San Raffaele

Corresponding Author:[email protected]

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Abstract

Adoptive regulatory T cell (Treg) trasfer represents a potential therapeutic option to control immune responses in organ transplantation, graft vs host disease, and autoimmunity, including type 1 diabetes. Treg for adoptive therapy are traditionally sorted and expanded in vitro with high doses of IL-2, showing stability and suppressive capacity, but with some limitations in terms of long-term survival once infused in patients. Here, we tested a novel expansion protocol in which we added IL-7 (IL-7 method, IL-7M) to the traditional standard method (StM) using IL-2. We showed that naïve Treg express significant levels of CD127 and robustly respond to IL-7 by phosphorylating STAT-5. Naive Treg expanded with the IL-7M were highly enriched in CD45RA +CD62L +CD95 + showing a reduction in the final cell yield and suppressive function. Treg expanded with the IL-7M preserved telomere length and were more resistant to cytokine withdrawal and fas-mediated apoptosis. Overall our data indicate that it is possible to expand naïve Treg in the presence of IL-7 to generate a final Treg product enriched in poorly differentiated CD45RA + cells and with better resistance to stress and apoptosis, potentially improving the long-term survival of Treg in adoptive transfer protocols.
26 Jul 20231st Revision Received
04 Aug 2023Submission Checks Completed
04 Aug 2023Assigned to Editor
04 Aug 2023Review(s) Completed, Editorial Evaluation Pending
14 Aug 2023Reviewer(s) Assigned
18 Aug 2023Editorial Decision: Accept