Robert A Good, Bing-Yan Wang, Nagwa S El-Badri, Ann Steele, Tazim Verjee
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When severe aplastic anemia complicated the first BMT which was performed to cure a fatal severe combined immunodeficiency, a second BMT cured for the first time a complicating severe aplastic anemia. Subsequently, BMT has been used effectively to treat some 75 otherwise fatal diseases such as resistant leukemias, lymphomas, inborn errors of metabolism, and genetic anomalies of the hematopoietic development such as sickle cell anemia, thalassemia, congenital neutropenias, and many other diseases. More recently, we have employed BMT in mice both to cure and cause autoimmunities, and, together, these experiments showed that autoimmunities actually reside in the hematopoietic stem cells. We have also found that mixed BMT or mixed hematopoietic stem cell transplantation (HSCT) can be used to prevent and cure the most complex autoimmunities such as those occurring in BXSB mice and in (NZW x BXSB)F1 W/BF1 mice. Untreated, the former develop fulminating lethal glomerulonephritis plus numerous humoral autoimmunities. Mice of the (W/B)F1 strain develop autoimmune thrombocytopenic purpura, coronary vascular disease with myocardial infarction, glomerulonephritis, and numerous autoantibodies. All of these abnormalities are prevented or cured by mixed syngeneic (autoimmune) plus allogeneic (normal healthy) BMT or mixed peripheral blood HSCT. 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引用次数: 9
摘要
将免疫缺陷疾病解释为“自然实验”的科学分析表明,特异性免疫系统由提供细胞介导免疫的T细胞以及产生和分泌抗体的B细胞和浆细胞组成。这两个独立的细胞系统定期相互作用,形成协调的防御,使哺乳动物能够在威胁个体完整性和生存的微生物海洋中生存。我们已经证明骨髓移植(BMT)可以作为细胞工程的一种形式来构建或重建免疫系统,并治愈其他致命的严重联合免疫缺陷。第一次BMT是为了治疗致命的严重联合免疫缺陷而进行的,第二次BMT首次治愈了严重再生障碍性贫血。随后,BMT已被有效地用于治疗大约75种其他致命疾病,如耐药白血病、淋巴瘤、先天性代谢错误和造血发育的遗传异常,如镰状细胞性贫血、地中海贫血、先天性中性粒细胞减少症和许多其他疾病。最近,我们在小鼠身上使用BMT来治疗和引起自身免疫,这些实验表明,自身免疫实际上存在于造血干细胞中。我们还发现混合BMT或混合造血干细胞移植(HSCT)可用于预防和治疗最复杂的自身免疫,如BXSB小鼠和(NZW x BXSB)F1 W/BF1小鼠。未经治疗,前者发展为暴发性致死性肾小球肾炎并伴有大量体液自身免疫。(W/B)F1菌株小鼠可发生自身免疫性血小板减少性紫癜、冠状动脉血管疾病伴心肌梗死、肾小球肾炎和大量自身抗体。所有这些异常都可以通过混合的同基因(自身免疫)和异体(正常健康)BMT或混合外周血HSCT来预防或治愈。因此,在实验动物中,最复杂的自身免疫性疾病可以通过产生稳定的混合嵌合作为一种细胞工程形式的同种异体骨髓移植或造血干细胞移植来预防或治愈。
Mixed bone marrow or mixed stem cell transplantation for prevention or treatment of lupus-like diseases in mice.
Scientific analyses fortified by interpretations of immunodeficiency diseases as 'experiments of nature' have revealed the specific immune systems to be comprised of T cells subserving cell-mediated immunities plus B cells and plasma cells which produce and secrete antibodies. These two separate cellular systems regularly interact with each other to produce a coordinated defense which permits mammals to live within a sea of microorganisms that threaten the integrity and the survival of individuals. We have shown that bone marrow transplantation (BMT) can be used as a form of cellular engineering to construct or reconstruct the immune systems and cure otherwise fatal severe combined immunodeficiency. When severe aplastic anemia complicated the first BMT which was performed to cure a fatal severe combined immunodeficiency, a second BMT cured for the first time a complicating severe aplastic anemia. Subsequently, BMT has been used effectively to treat some 75 otherwise fatal diseases such as resistant leukemias, lymphomas, inborn errors of metabolism, and genetic anomalies of the hematopoietic development such as sickle cell anemia, thalassemia, congenital neutropenias, and many other diseases. More recently, we have employed BMT in mice both to cure and cause autoimmunities, and, together, these experiments showed that autoimmunities actually reside in the hematopoietic stem cells. We have also found that mixed BMT or mixed hematopoietic stem cell transplantation (HSCT) can be used to prevent and cure the most complex autoimmunities such as those occurring in BXSB mice and in (NZW x BXSB)F1 W/BF1 mice. Untreated, the former develop fulminating lethal glomerulonephritis plus numerous humoral autoimmunities. Mice of the (W/B)F1 strain develop autoimmune thrombocytopenic purpura, coronary vascular disease with myocardial infarction, glomerulonephritis, and numerous autoantibodies. All of these abnormalities are prevented or cured by mixed syngeneic (autoimmune) plus allogeneic (normal healthy) BMT or mixed peripheral blood HSCT. Thus, the most complex autoimmune diseases can be prevented or cured in experimental animals by mixed syngeneic plus allogeneic BMT or HSCT which produce stable mixed chimerism as a form of cellular engineering.