Keratinocyte growth factor facilitates alloengraftment and ameliorates graft-versus-host disease in mice by a mechanism independent of repair of conditioning-induced tissue injury.

摘要: We have previously shown that pretreatment of mice with keratinocyte growth factor (KGF), an epithelial tissue repair factor, can ameliorate graft-versus-host disease (GVHD) after intensive chemoradiotherapeutic conditioning and allogeneic bone marrow transplantation (BMT). To determine whether this effect was dependent on a KGF-mediated mechanism affecting conditioning-induced cell injury, we studied GVHD in the absence using BALB/c severe combined immune-deficient (SCID) recipients given C57BL/6 T cells. KGF (5 mg/kg per day, subcutaneously) either before or T-cell transfer enhanced body weights extended survival. KGF-treated had elevated serum levels Th2 cytokine interleukin 13 (IL-13) day 6 concomitant reduced inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) interferon gamma (IFN-gamma). A 3-day also depressed secondary vitro mixed lymphocyte response (MLR) splenocytes taken 7 days vivo alloimmunization irradiated spleen would inhibit host-antidonor-mediated BM rejection, pan-T-cell-depleted cells were infused into sublethally administered BMT. Surprisingly, all schedules tested actually resulted alloengraftment. The presence receptor donor antihost alloreactive could not be detected by binding studies radiolabeled KGF, reverse transcriptase-polymerase chain reaction, Western blotting. Therefore, action inhibiting T-cell-mediated immune effects may due to direct These demonstrate mechanisms independent has great potential as anti-GVHD therapeutic agent added benefit rejection allografts. (Blood. 2000;96:4350-4356)