Author: Fisher JD, Zhang W, Balmert SC, Aral AM, Acharya AP, Kulahci Y, Li J, Turnquist HR, Thomson AW, Solari MG, Gorantla VS, Little SR
Title: In situ recruitment of regulatory T cells promotes donor-specific tolerance in vascularized composite allotransplantation.
Summary: Vascularized composite allotransplantation (VCA) encompasses face and limb transplantation, but as with organ transplantation, it requires lifelong regimens of immunosuppressive drugs to prevent rejection. To achieve donor-specific immune tolerance and reduce the need for systemic immunosuppression, we developed a synthetic drug delivery system that mimics a strategy our bodies naturally use to recruit regulatory T cells (Treg) to suppress inflammation. Specifically, a microparticle-based system engineered to release the Treg-recruiting chemokine CCL22 was used in a rodent hindlimb VCA model. These “Recruitment-MP” prolonged hindlimb allograft survival indefinitely (>200 days) and promoted donor-specific tolerance. Recruitment-MP treatment enriched Treg populations in allograft skin and draining lymph nodes and enhanced Treg function without affecting the proliferative capacity of conventional T cells. With implications for clinical translation, synthetic human CCL22 induced preferential migration of human Treg in vitro. Collectively, these results suggest that Recruitment-MP promote donor-specific immune tolerance via local enrichment of suppressive Treg.
Source: Sci Adv. 2020 Mar 13;6(11):eaax8429. doi: 10.1126/sciadv.aax8429. eCollection 2020 Mar.