Effects of IFN-γ on Pulmonary GVHD after Allo-Hematopoietic Stem Cell Transplantation

Abstract

To explore the effects of IFN-γ on pulmonary GVHD after hematopoietic stem cell transplantation (HSCT). The mouse GVHD models were established by using C57BL/6J, B6D2F1 mice and different HSCT. According to HSCT modes, the mice were divided into 3 groups: syngeneic HSCT group(C57BL/6J→C57BL/6J), allogeneic HSCT group (C57BL/6J→B6D2F1) and IFN-γ -/- allogeneic HSCT group (IFN-γ -/-→C57BL/6J→B6D2F1). The survival time, GVHD clinical seore, pulmonary pathologic changes in 3 groups were compared and analyzed, and the total cell count in BALF and IFN-γ level in serum were detected in 3 groups after transplantation. The mice in syngeneic HSCT group all survived at day 42 after transplantation without GVHD symptoms in lung, the GVHD clinical score was low. The mice in allogeneic HSCT group survived at day 24 after transplantation (survial rate >50%), the GVHD clinical score was higher than that in syngeneic HSCT group, the pathologic changes in lung did not serious, though the GVHD presentation was observed, but the olveola bleeding and lymphocyte infiltration in lung tissue were observed at day 28 after transplantation. The mice in IFN-γ -/- allogeneic HSCT group all died of lethal GVHD within 14 days after transplantation, the GVHD clinical score reached to 6.7± 0.83 at 1st week after tansplantation, which was significantly higher than that in syngeneic and allogeneic HSCT groups. At 1st week after transplantation, the serious GVHD pathological changes occured in lung tissue, total cell count in BALF significanty increased, compared with syngeneic and allogeneic HSCT groups, but IFN-γ level in serum was significantly lower than that in syngeneic and allogeneic HSCT groups (P<0.05). Donor-derived IFN-γ plays an important immunoprotective role for lung tissue after HSCT.