Presentation Title

The role of human beta-defensin-3 on regulatory T cell production in Graft-versus-Host disease prevention

Faculty Mentor

Brian Betts MD

Start Date

23-11-2019 10:45 AM

End Date

23-11-2019 11:30 AM

Location

56

Session

poster 4

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Graft-versus-host disease (GVHD) is a life threatening complication that affects over 30% of patients treated with allogeneic hematopoietic cell transplantation (allo-HCT). Conventional immunosuppressive drugs used in GVHD prophylaxis are broadly suppressive and impair graft-versus-leukemia (GVL) effects. Alternatively, cell therapy with regulatory T cells (Tregs) can prevent GVHD and spare anti-tumor benefits of allo-HCT. Beta-defensins are antimicrobial peptides that have anti-inflammatory properties, in part due to their effects on Treg function. Specifically, human beta-defensin-3 (hBD3) is produced by activated keratinocytes and protects the epithelial-barrier from pathogenic bacteria. Using allogeneic mixed lymphocyte reactions, we show that hBD3 fully polarizes Treg generation, eliminates alloreactive conventional T cells (Tconv), and significantly increases the Treg:Tconv ratio; which is a clinically relevant metric in controlling GVHD. Additionally, hBD3 significantly suppresses the proliferation of allo-stimulated T cells, deleting critical mediators of GVHD, as well as enhances the suppressive function of hBD3-treated Tregs. As such, we are able to rapidly produce pure human Tregs in less than 7 days. Thus, hBD3 presents a promising compound to selectively target alloreactive conventional T cells and preserve regulatory T cell populations essential in GVHD prevention.

Keywords: Graft-versus-Host-Disease, Beta-Defensin, Regulatory-T cell, Allogeneic hematopoietic cell transplantation

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Nov 23rd, 10:45 AM Nov 23rd, 11:30 AM

The role of human beta-defensin-3 on regulatory T cell production in Graft-versus-Host disease prevention

56

Graft-versus-host disease (GVHD) is a life threatening complication that affects over 30% of patients treated with allogeneic hematopoietic cell transplantation (allo-HCT). Conventional immunosuppressive drugs used in GVHD prophylaxis are broadly suppressive and impair graft-versus-leukemia (GVL) effects. Alternatively, cell therapy with regulatory T cells (Tregs) can prevent GVHD and spare anti-tumor benefits of allo-HCT. Beta-defensins are antimicrobial peptides that have anti-inflammatory properties, in part due to their effects on Treg function. Specifically, human beta-defensin-3 (hBD3) is produced by activated keratinocytes and protects the epithelial-barrier from pathogenic bacteria. Using allogeneic mixed lymphocyte reactions, we show that hBD3 fully polarizes Treg generation, eliminates alloreactive conventional T cells (Tconv), and significantly increases the Treg:Tconv ratio; which is a clinically relevant metric in controlling GVHD. Additionally, hBD3 significantly suppresses the proliferation of allo-stimulated T cells, deleting critical mediators of GVHD, as well as enhances the suppressive function of hBD3-treated Tregs. As such, we are able to rapidly produce pure human Tregs in less than 7 days. Thus, hBD3 presents a promising compound to selectively target alloreactive conventional T cells and preserve regulatory T cell populations essential in GVHD prevention.

Keywords: Graft-versus-Host-Disease, Beta-Defensin, Regulatory-T cell, Allogeneic hematopoietic cell transplantation