Donor T Cell Independent Mechanism is Critical for Mediating Steroid Refractory Gvhd in Murine Models

Acute graft-versus-host disease (GVHD) is a major complication of allogeneic cell transplantation (Allo-HCT). Steroids have remained the first line therapy for acute GVHD. However, 30-50% of patients develop steroid refractory GVHD (SR-GVHD) which shows extremely poor prognosis. The development of therapies for SR-GVHD is limited by an incomplete understanding of its pathophysiology because of the lack of clinical animal models. Here we generated SR-GVHD murine models by developing a major histocompatibility (MHC) matched, multiple minor histocompatibility antigens (miHAs) mismatched as well as an MHC mismatched haploidentical murine bone marrow transplantation (BMT) models and determined whether donor T cells are crucial role in mediating SR-GVHD.