Establishment of Acute GVHD Mouse Model of Haplo identical Hematopoietic Stem Cell Transplantation and Its Pathogenesis / 中国实验血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To establish the acute graft-versus-host disease(GVHD) mouse model based on haplo identical hematopoietic stem cell transplantation (HSCT) and to further investigate the pathogenesis of GVHD.</p><p><b>METHODS</b>Recipient mice ([C57BL/6×CBA/Ca]F1(H-2)) received lethal irradiation (11 Gy) of γ ray (Cs), followed by transplantation with donor-derived [C57BL/6(H-2)] T cell-depleted bone marrow cells (TD-BM) with or without donor-derived T cells. Recipients were randomly divided into 4 groups, including irradiation group, TD-BM group, TD-BM+T cell group 1 and TD-BM+T cell group 2. Survival rate and weight change were detected after HSCT. Pathological scoring were performed on the collected organs from recipients on day 14. Moreover, bone marrow chimerism was detected on days 14 and 18 after HSCT. Additionally, differentiation of donor-derived T cells towards Th1 cells in vivo was analyzed by flow cytometry. Furthermore, proliferation of donor-derived T cells in vivo was tested using CFSE.</p><p><b>RESULTS</b>The average survival in TD-BM, irradiation, TD-BM+T cell group 1 and TD-BM+T cell groups 2 were 60, 13.29±5.50, 33±2.3 and 29.14±1.77 days, respectively. On day 14 after transplantation, recipients of TD-BM + T cell group 1 displayed significantly more severe pathology in liver, colon, lung and skin. On days 14 and 28 after HSCT, bone marrow chimerism in recipients of both TD-BM group and TD-BM+ T cell groups 1 was over 94%. On day 14 after HSCT, serum cytokines IFN-γ, TNF-α and IL-1 levels in TD-BM+T cell group 1 were significantly higher than those in TD-BM group. Percentage of H-2bH-2kCD4IFN-γin spleen cells of recipients in TD-BM+T cell group 1 was higher than that of TD-BM group, with (0.5240±0.08447)% vs (7.912±0.6087)% (P<0.05). On days 14 after HSCT, donor-derived T cells displayed obvious proliferation in vivo.</p><p><b>CONCLUSION</b>C57BL/6(H-2)→［C57BL/6×CBA/Ca］F1(H-2) HSCT model can be used as a aGVHD model of haploidentical HSCT. Additionally, Th1 may play an important role in the pathogenesis of aGVHD resulting from haplo-identical HSCT.</p>