A Radio-Resistant Perforin-Expressing Lymphoid Population Controls Allogeneic T Cell Engraftment, Activation, and Onset of Graft-versus-Host Disease in Mice

Abstract

Immunosuppressive pretransplantation conditioning is essential for donor cell engraftment in allogeneic bone marrow transplantation (BMT). The role of residual postconditioning recipient immunity in determining engraftment is poorly understood. We examined the role of recipient perforin in the kinetics of donor cell engraftment. MHC-mismatched BMT mouse models demonstrated that both the rate and proportion of donor lymphoid cell engraftment and expansion of effector memory donor T cells in both spleen and BM weresignificantly increased within 5 to 7 days post-BMT in perforin-deficient (pfn-/-) recipients, compared with wild-type. In wild-type recipients, depletion of natural killer (NK) cell..