In situ recruitment of regulatory T cells promotes donor-specific tolerance in vascularized composite allotransplantation.

Sci Adv 2020 03 13;6(11):eaax8429. Epub 2020 Mar 13.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.

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 (T) to suppress inflammation. Specifically, a microparticle-based system engineered to release the T-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 T populations in allograft skin and draining lymph nodes and enhanced T function without affecting the proliferative capacity of conventional T cells. With implications for clinical translation, synthetic human CCL22 induced preferential migration of human T in vitro. Collectively, these results suggest that Recruitment-MP promote donor-specific immune tolerance via local enrichment of suppressive T.

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.aax8429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069700PMC
March 2020

Publication Analysis

Top Keywords

donor-specific tolerance
8
vascularized composite
8
immune tolerance
8
donor-specific immune
8
regulatory cells
8
composite allotransplantation
8
prolonged hindlimb
4
hindlimb allograft
4
"recruitment-mp" prolonged
4
model "recruitment-mp"
4
hindlimb vca
4
vca model
4
allograft survival
4
survival indefinitely
4
promoted donor-specific
4
tolerance recruitment-mp
4
days promoted
4
>200 days
4
indefinitely >200
4
mimics strategy
4

Similar Publications