Prevention of Graft Versus Host Disease by Inactivation of Host Antigen-Presenting Cells

TLDR

Graft‑versus‑host disease, a major toxicity of allogeneic bone marrow transplantation, results from donor T‑cell attacks on host tissues, yet the initial activation mechanism remains unclear. The study aims to develop strategies that inactivate host antigen‑presenting cells to prevent graft‑versus‑host disease and expand the safety of allogeneic bone marrow transplantation. In a murine model, only host‑derived antigen‑presenting cells trigger graft‑versus‑host disease, even when donor APCs are abundant.

Abstract

Graft versus host disease, an alloimmune attack on host tissues mounted by donor T cells, is the most important toxicity of allogeneic bone marrow transplantation. The mechanism by which allogeneic T cells are initially stimulated is unknown. In a murine allogeneic bone marrow transplantation model it was found that, despite the presence of numerous donor antigen-presenting cells, only host-derived antigen-presenting cells initiated graft versus host disease. Thus, strategies for preventing graft versus host disease could be developed that are based on inactivating host antigen-presenting cells. Such strategies could expand the safety and application of allogeneic bone marrow transplantation in treatment of common genetic and neoplastic diseases.