Effect of disease stage on clinical outcome after syngeneic bone marrow transplantation for relapsing experimental autoimmune encephalomyelitis
Effect of disease stage on clinical outcome after syngeneic bone marrow transplantation for relapsing experimental autoimmune encephalomyelitis
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DOI：
10.1182/blood.v91.7.2609.2609_2609_2616
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发表时间：
1998-04-01
期刊：
影响因子：
20.3
通讯作者：
Miller, SD
中科院分区：
文献类型：
--
作者：
Burt, RK;Padilla, J;Miller, SD
复发性实验性自身免疫性脑脊髓炎（R-EAE）是一种免疫介导的中枢神经系统脱髓鞘疾病。在急性疾病高峰期（第14天）进行骨髓消融和同基因骨髓移植（SBMT）可预防神经胶质疤痕形成并改善疾病严重程度。相比之下，当在慢性期晚期（第78天）进行同基因BMT时，仍然存在显着的胶质疤痕，并且临床严重程度与对照组没有显着差异。在疾病的急性或慢性阶段SBMT后，移植后免疫系统仍然对髓磷脂表位有反应，如通过体外增殖和干扰素-γ（IFN-γ）产生所确定的。然而，在接受SBMT的小鼠中，体内迟发型超敏反应（DTH）显著降低，而IFN-γ RNA水平和CNS内的炎性浸润略有改善。我们的结论是，SBMT未能改善临床疾病时，在慢性期进行可能是由于预先存在的胶质瘢痕。我们还得出结论，在没有神经胶质瘢痕形成和不可逆的神经元损伤，在体内DTH反应和组织学是更好的预测临床改善比在体外增殖或IFN-γ细胞因子的产生。(C)1998年，美国血液学会。
Relapsing experimental autoimmune encephalomyelitis (R-EAE) is an immune-mediated demyelinating central nervous system (CNS) disease. Myeloablation and syngeneic bone marrow transplantation (SBMT), when performed at the peak of acute disease (day 14), prevented glial scarring and ameliorated the disease severity. In contrast, when syngeneic BMT was performed late in chronic phase (day 78), significant glial scarring remained and the clinical severity did not differ significantly from that of the controls. After SBMT in either the acute or chronic phase of disease, the posttransplant immune system remained responsive to myelin epitopes as determined by in vitro proliferation and interferon-gamma (IFN-gamma) production. However, in mice undergoing SBMT, in vivo delayed-type hypersensitivity (DTH) responses were significantly decreased while IFN-gamma RNA levels and inflammatory infiltrates: within the CNS were slightly improved. We conclude that failure of SBMT to improve the clinical disease when performed in chronic phase may be due to preexisting glial scarring. We also conclude that in the absence of glial scarring and irreversible neuronal injury, in vivo DTH responses and histology are better predictors of clinical improvement than in vitro proliferation or IFN-gamma cytokine production. (C) 1998 by The American Society of Hematology.