دورية أكاديمية
Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance
| العنوان: | Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance |
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| المؤلفون: | Hirai, Toshihito, Ramos, Teresa L, Lin, Po-Yu, Simonetta, Federico, Su, Leon L, Picton, Lora K, Baker, Jeanette, Lin, Jian-Xin, Li, Peng, Seo, Kinya, Lohmeyer, Juliane K, Bolivar-Wagers, Sara, Mavers, Melissa, Leonard, Warren J, Blazar, Bruce R, Garcia, K Christopher, Negrin, Robert S |
| المصدر: | ISSN: 0021-9738 ; The journal of clinical investigation, vol. 131, no. 8 (2021) e139991. |
| سنة النشر: | 2021 |
| المجموعة: | Université de Genève: Archive ouverte UNIGE |
| مصطلحات موضوعية: | info:eu-repo/classification/ddc/616, Immunotherapy, Transplantation, Animals, Interleukin-2 / genetics, Interleukin-2 / immunology, Lymphocyte Activation, Mice, Inbred BALB C, Transgenic, Receptors, Signal Transduction / genetics, Signal Transduction / immunology, T-Lymphocytes, Regulatory / cytology, Regulatory / immunology, Transplantation Tolerance |
| الوصف: | Adoptive transfer of Tregs has been shown to improve alloengraftment in animal models. However, it is technically challenging to expand Tregs ex vivo for the purpose of infusing large numbers of cells in the clinic. We demonstrate an innovative approach to engineering an orthogonal IL-2/IL-2 receptor (IL-2R) pair, the parts of which selectively interact with each other, transmitting native IL-2 signals, but do not interact with the natural IL-2 or IL-2R counterparts, thereby enabling selective stimulation of target cells in vivo. Here, we introduced this orthogonal IL-2R into Tregs. Upon adoptive transfer in a murine mixed hematopoietic chimerism model, orthogonal IL-2 injection significantly promoted orthogonal IL-2R+Foxp3GFP+CD4+ cell proliferation without increasing other T cell subsets and facilitated donor hematopoietic cell engraftment followed by acceptance of heart allografts. Our data indicate that selective target cell stimulation enabled by the engineered orthogonal cytokine receptor improves Treg potential for the induction of organ transplantation tolerance. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33855972; https://archive-ouverte.unige.ch/unige:163970Test; unige:163970 |
| الإتاحة: | https://doi.org/10.1172/JCI139991Test https://archive-ouverte.unige.ch/unige:163970Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.1745D29F |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |