Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance
J Clin Invest. 2021 Apr 15;131(8):139991. doi: 10.1172/JCI139991.ABSTRACTAdoptive 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.PMID:33855972 | DOI:10.1172/JCI139991
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Toshihito Hirai Teresa L Ramos Po-Yu Lin Federico Simonetta Leon L Su Lora K Picton Jeanette Baker Jian-Xin Lin Peng Li Kinya Seo Juliane K Lohmeyer Sara B Wagers Melissa Mavers Warren J Leonard Bruce R Blazar K Christopher Garcia Robert S Negrin Source Type: research
More News: Bone Graft | Cancer | Cancer & Oncology | Cardiology | Heart | Heart Transplant | Lung Cancer | Lung Transplant | Transplants