We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance.
- Authors
Toshihito Hirai; Ramos, Teresa L.; Po-Yu Lin; Simonetta, Federico; Su, Leon L.; Picton, Lora K.; Baker, Jeanette; Jian-Xin Lin; Peng Li; Kinya Seo; Lohmeyer, Juliane K.; Wagers, Sara B.; Mavers, Melissa; Leonard, Warren J.; Blazar, Bruce R.; Garcia, K. Christopher; Negrin, Robert S.; Hirai, Toshihito; Lin, Po-Yu; Lin, Jian-Xin
- Abstract
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.
- Subjects
REGULATORY T cells; CYTOKINE receptors; T cells; TRANSPLANTATION of organs, tissues, etc.; INJECTIONS; IMMUNOLOGICAL tolerance; RESEARCH; INTERLEUKIN-2; ANIMAL experimentation; RESEARCH methodology; CELL receptors; IMMUNOLOGY technique; MEDICAL cooperation; EVALUATION research; CELLULAR signal transduction; COMPARATIVE studies; MICE
- Publication
Journal of Clinical Investigation, 2021, Vol 131, Issue 8, p1
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI139991