Wang Chun-Ling, Xu Kai-Lin, Pan Xiu-Ying, Du Bing
Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Zhonghua Xue Ye Xue Za Zhi. 2008 Feb;29(2):92-6.
To study the effect of delayed sequential bone marrow transplantation on acute graft-versus-host disease (aGVHD) in major H-2 incompatible mouse transplantation.
C57BL/6 (H-2b) mice were used as donors and BALB/c (H-2d) mice as recipients. BALB/c mice were given 8.0 Gys total body irradiation (TBI) on day 0 and infused with a blend of bone marrow cells and spleen cells in different time. Transplantation was carried out as follows: group I TBI on day 0 and transplantation at 4 h after TBI; groups of II TBI on day 0 and transplantation at 4 h, d1, d2, d3 after TBI; groups III TBI on day 0 and transplantation at day 4 after TBI; groups IV TBI on day 0 and transplantation at day 4 through day 7 after TBI. Recipient's spleen H-2b cells were detected by flow cytometry and the level of serum cytokines (IL-2, IL4, IL-6, IL-10 and IFN-gamma) by ELISA. The survival, aGVHD and hematopoietic recovery were observed.
aGVHD occurred in group I and the mice all died within 3 weeks after transplantation. The 60 day survival rates of groups of II and III were 30% and 50% respectively. The degree of aGVHD in group III was modest and the survival rate was higher than that in other groups (P <0.05). The peak time of IL-2, IFN-gamma, IL-4 and IL-10 in groups III and IV were later than that in group I. The levels of IL-4 and IL-10 in groups III and IV were higher than that in group I and for the levels of IL-2 and IFN-gamma were on the contrary (P < 0.05). The level of IL-6 in all groups peaked on day 5 to day 10 after TBI and was higher in group I than in others (P <0.05). In group IV the mean value of donor H-2b cells was (98.1 +/- 1.1)% on day 60 and WBC counts recovered normal on day 20.
Delayed sequential transplantation can reduce the morbidity of aGVHD ,improve the survival rate and not affect the engraftment and reconstitution of hematopoiesis in mouse allo-BMT. The mechanism of aGVHD prevention may be related to the reducing of type 1 cytokines of T lymphocyte and the increasing of type 2 cytokines.
研究延迟序贯骨髓移植对主要组织相容性复合体Ⅱ类分子（MHCⅡ）不相合小鼠移植中急性移植物抗宿主病（aGVHD）的影响。
以C57BL/6（H-2b）小鼠为供体，BALB/c（H-2d）小鼠为受体。于第0天给BALB/c小鼠全身照射8.0 Gy，在不同时间输注骨髓细胞和脾细胞混合液。移植方式如下：Ⅰ组于第0天全身照射，照射后4小时移植；Ⅱ组于第0天全身照射，照射后4小时、第1天、第2天、第3天移植；Ⅲ组于第0天全身照射，照射后第4天移植；Ⅳ组于第0天全身照射，照射后第4天至第7天移植。通过流式细胞术检测受体脾脏H-2b细胞，采用酶联免疫吸附测定法（ELISA）检测血清细胞因子（白细胞介素-2、白细胞介素-4、白细胞介素-6、白细胞介素-10和γ干扰素）水平。观察小鼠的存活情况、aGVHD及造血恢复情况。
Ⅰ组发生aGVHD，小鼠均在移植后3周内死亡。Ⅱ组和Ⅲ组60天生存率分别为30%和50%。Ⅲ组aGVHD程度较轻，生存率高于其他组（P<0.05）。Ⅲ组和Ⅳ组白细胞介素-2、γ干扰素、白细胞介素-4和白细胞介素-10的峰值时间晚于Ⅰ组。Ⅲ组和Ⅳ组白细胞介素-4和白细胞介素-10水平高于Ⅰ组，而白细胞介素-2和γ干扰素水平则相反（P<0.05）。所有组白细胞介素-6水平在照射后第5天至第10天达到峰值，Ⅰ组高于其他组（P<0.05）。Ⅳ组第60天供体H-2b细胞平均值为（98.1±1.1）%，白细胞计数在第20天恢复正常。
延迟序贯移植可降低小鼠异基因骨髓移植中aGVHD的发病率，提高生存率，且不影响造血植入和造血重建。预防aGVHD的机制可能与T淋巴细胞1型细胞因子减少和2型细胞因子增加有关。
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