Recruitment of Regulatory T Cells Promotes Donor-Specific Tolerance in Vascularized Composite Allotransplantation

J. D. Fisher¹, W. Zhang², S. C. Balmert³, A. M. Aral¹, Y. Kulahci⁴, A. P. Acharya⁴, J. Li², H. R. Turnquist⁵, A. W. Thomson⁵, M. G. Solari², V. S. Gorantla⁶, S. R. Little⁴

¹Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, ²Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, ³Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, ⁴Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, ⁵Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, ⁶Department of Bioengineering, Wake Forest University, Winston-Salem, NC

Meeting: 2020 American Transplant Congress

Abstract number: 506

Keywords: Bioengineering, Tolerance

Session Information

Session Name: Vascularized Composite Allograft

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:45pm

Presentation Time: 3:27pm-3:39pm

Location: Virtual

*Purpose: Vascularized composite allotransplantation (VCA) encompasses face and limb transplantation, but as with organ transplantation, it requires lifelong regimens of immunosuppressive drugs to prevent rejection.

*Methods: 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. Three doses of Recruitment-MP (9mg, 50mg and 100mg) were tested.

*Results: The 50mg Recruitment-MP dose prolonged hindlimb allograft survival indefinitely (over 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

*Conclusions: 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.

To cite this abstract in AMA style:

Fisher JD, Zhang W, Balmert SC, Aral AM, Kulahci Y, Acharya AP, Li J, Turnquist HR, Thomson AW, Solari MG, Gorantla VS, Little SR. Recruitment of Regulatory T Cells Promotes Donor-Specific Tolerance in Vascularized Composite Allotransplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/recruitment-of-regulatory-t-cells-promotes-donor-specific-tolerance-in-vascularized-composite-allotransplantation/. Accessed November 22, 2024.

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