中国肿瘤生物治疗杂志2012，Vol.19Issue(1)：56-60,5.DOI:10.3872/j.issn.1007-385X.2012.01.010
阻断诱导型共刺激分子信号通路对小鼠急性移植物抗宿主病的影响
Effect of blocking inducible costimulatory signaling pathway on mouse model of acute graft-versus-host disease
摘要
Abstract
Objective; To block inducible costimulator(IC0S)-B7H signal with ICOS-Ig fusion protein and study the effect of IC0S-B7H signal on mouse model of acute graft-versus-host disease (aGVHD). Methods; Allogeneic aGVHD model was established with lethally irradiated BALB/c recipients receiving allogeneic BM and spleen T cells from C57BL/ 6 with 100 (xg ICOS-Ig intraperitoneally 4 times at d 0, 2, 4 and 6 of transplantation, with the same concentration of human Ig (h-Ig) as control. Survival, weight and GVHD status were monitored daily. At d 4 of transplantation, mice were sacrificed and the spleens were removed and homogenized, and the division of donor T cells was assessed by CFSE intensity of H-2Kd negative, and CD4 or CD8 positive cells. H-2Kd~ negative, CD4 and CD8 positive spleen T cell populations at d 10 of transplantation were stained with annexin-V and PI for evaluating the apoptosis rate. Results; Block ICOS-B7H pathway effectively controlled severe aGVHD in the control group. The median survival time was (10 ±2.4) days in h-Ig group over (20 ± 3. 1) days in ICOS-Ig group( P -0. 0217, n = 14). Pathologic evaluation revealed that the hepatic portal and intestinal mucosa in ICOS-Ig group had less lymphocyte infiltration and tissue damage than did those in the control group. ICOS-Ig had no obvious effect on allogeneic T cell proliferation (h-Ig: 98.88 ±0.76, ICOS-Ig: 99.71 ±0.27 in CD4* T cells, h-Ig: 98.62 ±0. 63, ICOS-Ig: 99. 53 ±0. 51 in CD8+ T cells by CFSE tracing assay at d 3) , but increased apoptosis of allogeneic CD8+T cells in GVHD model at d 10: h-Ig: 15.72 ±7.34, ICOS-Ig: 22.78 ±6.94 inCD4+ T cells (P=0.078,ra =5); h-Ig: 15.7 ±9.59, ICOS-Ig: 25. 92 ±5. 66 in CD8+ T cells (P =0. 032,n =5). Conclusion; Block ICOS-B7H pathway can prevent aGVHD through shortening the survival time of allo-T cells.关键词
诱导型共刺激分子/移植物抗宿主病/CD4+T淋巴细胞/CD8+T淋巴细胞/凋亡/血液肿瘤Key words
inducible costimulator (ICOS)/ graft-versus-host disease/ CD4+ T lymphocyte/ CD8 + T lymphocyte/ apoptosis/ hematopoietic malignancy分类
医药卫生引用本文复制引用
王继承,朱其聪..阻断诱导型共刺激分子信号通路对小鼠急性移植物抗宿主病的影响[J].中国肿瘤生物治疗杂志,2012,19(1):56-60,5.基金项目
国家自然科学基金资助项目(No.30871100). （No.30871100）
