Affiliation:
1. Transplant Immunology Lab San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele Milan Milan Italy
2. Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases Ospedale San Raffaele Scientific Institute Milan Italy
3. Vita‐Salute San Raffaele University Milan Italy
Abstract
AbstractAdoptive 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.
Funder
European Foundation for the Study of Diabetes
Juvenile Diabetes Research Foundation International
Subject
Immunology,Immunology and Allergy
Cited by
1 articles.
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