Bone-marrow transplantation: man and mouse
Bone-marrow transplantation: man and mouse
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骨髓移植：人和小鼠
DOI：
10.1038/280720a0
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发表时间：
1979
期刊：
影响因子：
64.8
通讯作者：
M. Robertson
中科院分区：
文献类型：
--
作者：
M. Robertson
在Hammersmith医院接受移植治疗再生障碍性贫血的13名存活患者最终恢复了完全的自体骨髓功能（EC Gordon-Smith，Hammersmith医院），这表明在这些患者中至少一些成功的移植的功能可能是使他们渡过难关，直到他们自发地恢复，其中一些人单独使用类固醇就能恢复。自发康复的比例到底有多高还不清楚：在西雅图的弗雷德哈钦森癌症中心的168例患者中，只有4例自发康复。在这些情况下，贫血是否是由一种清除非常缓慢的有毒物质引起的，或者是否是一种暂时的自身免疫问题尚不清楚。另一方面，在SCID中，成功移植的骨髓替代除了B细胞之外的所有细胞是很常见的（R。O 'Reilley，Sloan-Kettering，纽约），这表明宿主诱导的调节缺陷。目前还不清楚在哪个阶段骨髓分化在SCID中失败（R。Parkman，Children's Hospital Medical Center，Boston），这并不令人惊讶，因为尽管小鼠免疫学最近取得了进展，但免疫系统的个体发生仍不清楚。当然，一个核心问题是组织匹配，对此没有完全令人满意的测试。错配可能导致宿主对移植物的排斥，其中宿主是免疫活性的并且未实现完全抑制，或者导致移植物抗宿主病。B。Torok-Storb（Fred哈钦森癌症中心，西雅图）报道，在同种异体培养中，患者细胞对供体细胞增殖的抑制有助于预测移植失败，而D. Schendel（免疫学研究所，慕尼黑）报告了未显示不匹配血清学证据的相关供体细胞之间的阳性细胞毒性试验。一个更微妙的移植物排斥反应的来源，这是没有检测到这些测试是不了解的错配，将导致杂合子F1小鼠排斥亲本骨髓，虽然他们将接受皮肤移植。G. Cudkowicz（布法罗医学院的州立大学）报告说，来自F1小鼠的细胞虽然不能裂解亲本品系靶细胞，但仍能在体外与它们结合，并表明这可能与它们的细胞毒性潜力有关。这种微妙的影响是否在人类患者的骨髓排斥中起重要作用还不清楚。虽然总的来说，在MHC错配的骨髓移植成功的机会很低，但也有一些显着的成功报告（O 'Reilley & R。Storb，Fred哈钦森癌症中心，西雅图）。这可能是因为某些MHC抗原比其他抗原更重要：W。埃尔金斯（宾夕法尼亚大学）发现，为了尽量减少小鼠的移植物抗宿主病，更重要的是匹配！区域抗原（人DR抗原的小鼠等效物）比K或D抗原（人A和B抗原的小鼠等效物）更显著。另一种可能性是血清学错配可能并不总是个体病例中强T细胞反应的可靠指标。鉴于完美的组织匹配几乎是不可能的，而且除了单卵双胞胎之外，次要移植抗原的错配总是会导致移植物抗宿主病，那么在骨髓移植之前，是否可以采取任何措施来去除会对宿主产生反应的细胞？许多努力已经投入到确定的细胞的身份问题，和S。Theirfelder（Institute of Haematology，GSF，慕尼黑）和W. Muller-Ruchholz（基尔大学）都对它们作为T细胞的鉴定做出了贡献。J·斯普伦特
surviving patients out of thirteen given transplants for aplastic anaemia at the Hammersmith Hospital eventually recovered full autologous bone-marrow function(EC Gordon-Smith, Hammersmith Hospital) which suggests that the function of at least some successful transplants in such patients may be to tide them over until they spontaneously recover, which some of them do on steroids alone. Exactly how high the proportion of spontaneous recoveries may be is not clear: of a series of 168 at the Fred Hutchinson Cancer Center in Seattle, only four spontaneously recovered. Whether in these cases the anaemia is caused by a toxic substance which clears only very slowly, or whether it is a temporary autoimmine problem is not known. In SCID, on the other hand, it is quite common for successfully transplanted bone marrow to replace everything but B cells (R. O'Reilley, Sloan-Kettering, New York), which suggests a regulatory defect induced by the host. It is unclear at what stage bone-marrow differentiation fails in SCID (R. Parkman, Children's Hospital Medical Center, Boston) and this is hardly surprising since in spite of recent advances in mouse immunology, the ontogeny ofthe immune system is not understood. A central problem is of course tissue matching, for which there is no entirely satisfactory test. A mismatch may lead either to the rejection of the graft by the host, where the host is immunocompetent and complete suppression is not achieved, or to graft-versus-host disease. B. Torok-Storb (Fred Hutchinson Cancer Center, Seattle) reported that the inhibition of donor cell proliferation by the patient's cells in allogeneic cultures could help to predict graft failure, while D. Schendel (Institute of Immunology, Munich) reported positive cytotoxicity tests between the cells of related donors who showed no serological evidence of mismatch. An even more subtle source of graft rejection which is not detected by either of these tests is the ill-understood mismatch that will lead heterozygous F 1 mice to reject parental bone marrow though they will accept skin grafts. G. Cudkowicz (State University of Buffalo School of Medicine) reported that cells from the F 1 mice which did not lyse parental-strain targets could nonetheless be shown to bind to them in vitro, and suggested that this might correlate with their cytotoxic potential. Whether such subtle effects play any significant part in marrow rejection in human patients is unclear. Although on the whole the chances of success for bone-marrow transplants across MHC mismatches are low, there have been reports of some remarkable successes (O'Reilley & R. Storb, Fred Hutchinson Cancer Center, Seattle). This may be because some MHC antigens are more important than others: W. Elkins (University of Pennsylvania) finds that to minimise graft-versus-host disease in mice it is more important to match for!-region antigens (the mouse equivalent of the human DR antigens) than for K or D antigens (the mouse equivalent of the human A and B antigens). The other possibility is that serological mismatches may not always be a reliable indicator of a strong T cell reponse in an individual case. Given that perfect tissue matching will almost never be possible, and that mismatching of minor transplantation antigens will always cause graft-versus-host disease except in monozygotic twins, can anything be done to remove the cells that will react against the host before the bone marrow is transplanted? Much effort has gone into establishing the identity of the cells in question, and S. Theirfelder (Institute of Haematology, GSF, Munich) and W. MUller-Ruchholz (Kiel University) have both contributed to their identification as T cells. J. Sprent …