Effects of Pre-conditioning Dose on the Immune Kinetics and Cytokine Production in the Leukocytes Infiltrating GVHD Tissues after MHC-matched Transplantation

BACKGROUND: Graft-versus-host disease (GVHD) is a huddle for success of hematopoietic stem cell transplantation. In this study, effects of irradiation dose on immune kinetics of GVHD were investigated using B6 → BALB.B system, a mouse model for GVHD after MHC-matched allogeneic transplantation. METHODS: BALB.B mice were transplanted with bone marrow and spleen cells from C57BL/6 mice after irradiation with different doses. Leukocytes residing in the peripheral blood and target organs were collected periodically from the GVHD hosts for analysis of chimerism formation and immune kinetics along the GVHD development via flow cytometry. Myeloid cells were tested for production of IL-17 via flow cytometry. RESULTS: Pre-conditioning of BALB.B hosts with 900 cGy and 400 cGy resulted in different chimerism of leukocytes from the blood and affected survival of GVHD hosts. Profiles of leukocytes infiltrating GVHD target organs, rather than profiles of peripheral blood leukocytes (PBLs), were significantly influenced by irradiation dose. Proportions of IL-17 producing cells in the infiltrating Gr-1(+) or Mac-1(+) cells were higher in the GVHD hosts with high does irradiation than those with low dose irradiation. CONCLUSION: Pre-conditioning dose affected tissue infiltration of leukocytes and cytokine production by myeloid cells in the target organs.