Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance

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

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Article numbere139991
JournalJournal of Clinical Investigation
Volume131
Issue number8
DOIs
Publication statusPublished - 15 Apr 2021
Externally publishedYes

Fingerprint

Dive into the research topics of 'Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance'. Together they form a unique fingerprint.

Cite this