Li Chao-Hong, Xu Kai-Lin, Pan Xiu-Ying, Du Bing
The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Zhonghua Xue Ye Xue Za Zhi. 2007 Feb;28(2):93-7.
To explore the in vitro effect on control of graft-versus-host disease (GVHD) and its mechanism in mice by blockade of CD137-CD137L pathway.
Responder spleen cells from BALB/c donor mice (H-2(d)) were incubated with stimulator spleen cells from C57BL/6 ( H-2(b)) recipient mice, with or without anti-CD137L mAb. Lethally irradiated C57BL/6 mice were transplanted with donor bone marrow cells plus primary MLC spleen T cells. Group A (Allo-BMT control group): allo-BMT mice not receiving any prevention measures for GVHD. Group B (CsA + MTX control group): CsA and MTX given to C57BL/6 mice after transplantation. Group C (experimental group): donor spleen cells from BALB/c mice treated with anti-CD137L mAb. The percentages of CD3+ CD8+ T and CD3+ CD4+ T cells in the three groups were detected by flow cytometry, and the level of cytokines (IFN-gamma, IL-2, IL-10, IL-4) by RT-PCR.
The incidence of GVHD in group C was 70%, while in group A and group B were 100%. The survival rate was higher and the median survival time was longer of group C than that of group A and B (P < 0.01). All mice in group A died of aGVHD within 15 ds, while 30% of mice in group C survived more than 30 ds. Symptoms and histological signs of GVHD in group C were the mildest among the three groups. The percentage of CD3+ CD8+ T cells and the levels of IFN-gamma were significantly lower (P < 0.01), and the levels of IL-10 were significantly higher in group C than those in group A and B (P < 0.01).
Treatment of donor T cells with anti-CD137L mAb in vitro may relieve GVHD, thereby improve the survival time and survival rate, which maybe related to increasing Th1 cytokine (IFN-gamma) and decreasing Th2 cytokine (IL-10) as well as reducing CD3+ CD8+ T cells.
探讨阻断CD137-CD137L通路对小鼠移植物抗宿主病（GVHD）的体外控制作用及其机制。
将BALB/c供体小鼠（H-2(d)）的反应性脾细胞与C57BL/6（H-2(b)）受体小鼠的刺激脾细胞共同培养，同时加入或不加入抗CD137L单克隆抗体。对C57BL/6小鼠进行致死性照射后，移植供体骨髓细胞和原代混合淋巴细胞培养脾T细胞。A组（异基因骨髓移植对照组）：未接受任何GVHD预防措施的异基因骨髓移植小鼠。B组（环孢素A+甲氨蝶呤对照组）：移植后给C57BL/6小鼠注射环孢素A和甲氨蝶呤。C组（实验组）：用抗CD137L单克隆抗体处理的BALB/c小鼠供体脾细胞。采用流式细胞术检测三组中CD3+CD8+T细胞和CD3+CD4+T细胞的百分比，采用逆转录聚合酶链反应检测细胞因子（IFN-γ、IL-2、IL-10、IL-4）水平。
C组GVHD发生率为70%，A组和B组为100%。C组的生存率更高，中位生存时间比A组和B组更长（P<0.01）。A组所有小鼠在15天内死于急性GVHD，而C组30%的小鼠存活超过30天。C组GVHD的症状和组织学表现是三组中最轻的。C组CD3+CD8+T细胞百分比和IFN-γ水平显著低于A组和B组（P<0.01），IL-10水平显著高于A组和B组（P<0.01）。
体外使用抗CD137L单克隆抗体处理供体T细胞可减轻GVHD，从而提高生存时间和生存率，这可能与增加Th1细胞因子（IFN-γ）、降低Th2细胞因子（IL-10）以及减少CD3+CD8+T细胞有关。
