Academic Journal
Interleukin-7 improves the fitness of regulatory T cells for adoptive transfer
| العنوان: | Interleukin-7 improves the fitness of regulatory T cells for adoptive transfer |
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| المؤلفون: | Cosorich I., Filoni J., Di Dedda C., Ferrari A., Jofra T., Cesarano S., Bonini C., Piemonti L., Monti P. |
| المساهمون: | Cosorich, I., Filoni, J., Di Dedda, C., Ferrari, A., Jofra, T., Cesarano, S., Bonini, C., Piemonti, L., Monti, P. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | IL-7, immunometabolism, regulatory T cells |
| الوصف: | Adoptive regulatory T-cell (Treg) transfer has emerged as a promising therapeutic strategy for regulating immune responses in organ transplantation, graft versus host disease, and autoimmunity, including Type 1 diabetes. Traditionally, Treg for adoptive therapy have been sorted and expanded in vitro using high doses of IL-2, demonstrating stability and suppressive capabilities. However, limitations in their long-term survival post-infusion into patients have been observed. To address this challenge, we investigated a novel expansion protocol incorporating interleukin-7 (IL-7) alongside the traditional method utilizing IL-2 (referred to as IL-7 method, IL-7M). Our study revealed that naïve Treg express significant levels of CD127 and display robust responsiveness to IL-7, characterized by STAT-5 phosphorylation. Expanding naïve Treg with the IL-7M protocol led to a substantial enrichment of CD45RA+ CD62L+ CD95+ Treg but showing a reduction in the final cell yield and suppressive function. Moreover, Treg expanded with the IL-7M exhibited preserved telomere length and demonstrated enhanced resistance to cytokine withdrawal and fas-mediated apoptosis. When transferred into NSG mice IL-7M-Treg persisted longer and reduced the expansion of T cells, but did not significantly reduce the severity of xenoGvHD. In conclusion, our data demonstrate the feasibility of expanding naïve Treg in the presence of IL-7 to generate a Treg product enriched in poorly differentiated CD45RA+ cells with enhanced survival capabilities. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37671510; info:eu-repo/semantics/altIdentifier/wos/WOS:001062232800001; volume:170; issue:4; firstpage:540; lastpage:552; numberofpages:13; journal:IMMUNOLOGY; https://hdl.handle.net/20.500.11768/151216 |
| DOI: | 10.1111/imm.13690 |
| الاتاحة: | https://hdl.handle.net/20.500.11768/151216 https://doi.org/10.1111/imm.13690 https://onlinelibrary.wiley.com/doi/10.1111/imm.13690 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.B80AB43E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/imm.13690 |
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