Significance of Th1/Th17 Imbalance in Mice with Acute Graft-versus-Host Disease / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Th1/Th17 cell imbalance on the pathogenesis of acute graft-versus-host disease (GVHD) in mice.</p><p><b>METHODS</b>In a murine GVHD model of C57BL/6 (H-2(b)), a low dose of halofuginone (HF) was applied for treating the recipients in order to result in Th1/Th17 imbalance. Rechipient mice were divided into GVHD group (without HF intervention) and GVHD plus HF group (treated by HF). The recipients were monitored for survival rate, clinical scores of acute GVHD, contents of circulatory Th1 and Th17 cells, Th1/Th17 ratio and serum level of IFN-γ and IL-17A. Expression levels of IFN-γ and IL-17A in target organs were analyzed by using real-time PCR, and the target organs were delivered for histological examinations.</p><p><b>RESULTS</b>Recipients treated with HF showed that all the mortality, circulatory Th1/Th17 ratio and clinical score were higher than those in the mice without HF intervention (P < 0.05). Circulatory Th1/Th17 ratio positively correlates with clinical score (P < 0.001). HF administration reduces the expression level of intestinal IL-17A and increases intrahepatic and intestinal IFN-γ level (P < 0.05), HF treatment aggravates GVHD in liver and small intestine with augmented hepatic and intestinal inflammation.</p><p><b>CONCLUSION</b>Th1/Th17 imbalance contributes to the pathogenesis of acute GVHD.</p>

Recovery of vascular niche in bone marrow by donor derived endothelial progenitor cells after allogeneic bone marrow transplantation in mice / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the role of endothelial progenitor cell (EPC) injection in the restoration of vascular niche in bone marrow (BM) after allo-BMT in mice, and to observe its role on hematopoietic reconstitution.</p><p><b>METHODS</b>6-8 weeks old female BALB/c (H-2(d)) were randomized to BMT (allo-BMT) group and combined EPC transplant (allo-BMT + EPC) group. For allo-BMT group, female BALB/c mice were lethally irradiated with 60Co source, and then were injected intravenously with 5×10(6) BM cells from donor mice. In allo-BMT + EPC group, recipient mice were injected intravenously with 5×10(6) BM cells and 5×10(5) EPC from donor mice. The recipients were monitored for histological changes of endothelial cells (EC) in BM. The recovery of hematopoiesis was determined by white blood cell counts and the proportion of reticulocytes in circulation and the proportion of hematopoietic stem cells (HSC) in BM. The histology of hematopoiesis in BM was also detected.</p><p><b>RESULTS</b>The in vitro induced EPC successfully homed to the bone marrow of recipients. The ECs of allo-BMT recipients were destructed severely, while the structures of ECs were restored in EPC treated recipients. 10 and 15 days after allo-BMT, the amount of Lin-c-kit(+)Sca-1(+) cells in the BM of the EPC treated group were (20.31 ± 2.65)×10(3) per mouse and (10.26 ± 2.19)×10(3) per mouse, while the allo-BMT group's were (9.61 ± 0.98)×10(3) per mouse and (4.09 ± 1.34)×10(3) per mouse; and 15 days after allo-BMT, the amount of white blood cell counts and proportion of reticulocytes of the EPC treated group were (1.20 ± 0.11)×10(9)/L and (2.35 ± 0.30)% comparing to the allo-BMT group which were (0.65 ± 0.10)×10(9)/L and (1.63 ± 0.20)%.</p><p><b>CONCLUSION</b>Co-transfer of donor EPC restores the ECs of bone marrow, which consequently promotes hematopoietic reconstitution in murine allo-BMT.</p>

The role of Th17 cells in early onset of mice acute graft versus host disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the role of Th17 cells in early onset of acute graft-versus-host disease (aGVHD) and its mechanism.</p><p><b>METHODS</b>Mice aGVHD model was established by irradiated BABL/c mice inoculated with mixed suspension of C57BL/6 bone marrow cells and splenocytes. The mice were divided into 4 groups: (1) normal control, (2) irradiated group, (3) allo-BMT + DMSO group, (4) allo-BMT + halofuginone (HF) group. HF was given intraperitoneally at 5 µg per mouse from -1 d to +10 d after allogeneic bone marrow transplantation(allo-BMT).Mice aGVHD symptoms and survival were observed. Th1/Th17 cells ratio was evaluated by flow cytometry.</p><p><b>RESULTS</b>All the experimental groups (3) and (4) developed aGVHD after transplantation. More severe aGVHD was observed in group (4) than in group (3). HF prevented cutaneous aGVHD in all the mice, but augmented hepatic and small intestine GVHD. The percentage of Th17 cells and the ratio of Th1/Th17 were significantly higher while the percentage of Th1 cells was significantly lower in group (4) at day +6 (P < 0.05).</p><p><b>CONCLUSION</b>Early blockage of Th17 cell results in increase of Th1 cell percentage, which exacerbates aGVHD.</p>