Assessing Perforin-independent Granzyme B function in Acute Graft-Versus-Host Disease: Impact on Allogeneic Hematopoietic Cell Transplantation

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B736
Abstract ID: 5459

Presenting Author:
Raylynn S Thompson , Research Fellow at Univ. of Maryland, Baltimore

Abstract:

Challenging the conventional model of granule-mediated cytotoxicity, this study questions the dependency of Granzyme B (GzmB) function on Perforin (Prf1) in allogeneic immune response. Focused on understanding the role of Perforin-independent GzmB activity in acute graft-versus-host disease (GVHD), we employed a C57BL/6 to BALB/c allogeneic hematopoietic cell transplantation (allo-HCT) model. Transplanting various donor-derived cell populations, including WT, Prf1 knockout (KO), and Prf1-GzmB double KO, into lethally irradiated BALB/c host mice, we observed significantly reduced acute GVHD with Prf1 KO donor cells. Flow cytometry revealed equivalent GzmB expression in WT and Prf1 KO donor CD8+ and CD4+ T cells, yet Prf1-GzmB DKO did not further alleviate GVHD compared to Prf1 KO alone. Further experiments with purified T cells from Prf1 KO and Prf1-GzmB DKO donors showed no significant difference in inducing systemic acute GVHD. While highlighting the critical role of Prf1-dependent cytotoxic activity in systemic acute GVHD, our ongoing studies delve into specific organs and the chronic GVHD stage to explore potential impacts of Perforin-independent GzmB function. This research may significantly contribute to understanding allo-HCT for hematological disorders.