Poltorak M, Freed W J
Preclinical Neurosciences Section, National Institute of Mental Health Neuroscience Center, St. Elizabeth Washington, DC 20032.
Ann Neurol. 1991 Apr;29(4):377-88. doi: 10.1002/ana.410290408.
Embryonic brain tissue allografts under many circumstances survive transplantation into the brain. It is generally believed that such grafts will not survive if the host animal is systemically sensitized, by skin grafting or other means, to major histocompatibility complex (MHC) antigens of the donor animal. We have found that F344 brain grafts survive in BN hosts even when the host is systemically sensitized to F344 tissue. Embryonic cerebral neocortex from F344 donors was transplanted into BN host rats (n = 95). Subsequently, the host rats were systemically sensitized with donor skin (n = 25), brain tissue (n = 41), or spleen cells (n = 6) and compared with a control group of rats consisting of allografts with no sensitization or sham procedures (n = 23). Rejection of the transplants in BN rat hosts was not provoked by any of the sensitization methods tested. Minor immunological responses that did not result in rejection were, however, present in many host animals. We did not observe infiltration of W3/13+ T cells and OX8+ cytotoxic lymphocytes in any of the groups. Nevertheless, substantial infiltrations of OX6+ antigen-presenting cells and W3/25+ helper T cells were present. There was also an extensive enhancement of MHC class I immunoreactivity in parts of the grafted tissue developing within the third ventricle, but not for the same type of graft in the lateral ventricle. This increase of MHC class I expression was not accompanied by infiltration of cytotoxic T cells. Our findings thus suggest that neural graft rejection depends on general genetic susceptibility to immune reactions, particularly experimental allergic encephalomyelitis and not only on disparity between donor and host antigens encoded by the MHC. Moreover, enhancement of MHC class I and class II expression within transplanted tissue does not predict graft rejection.
在许多情况下,胚胎脑组织异体移植到大脑后能够存活。一般认为,如果宿主动物通过皮肤移植或其他方式对供体动物的主要组织相容性复合体(MHC)抗原产生全身致敏,那么这种移植组织将无法存活。我们发现,即使宿主对F344组织产生全身致敏,F344脑移植组织在BN宿主中仍能存活。将来自F344供体的胚胎大脑新皮质移植到BN宿主大鼠体内(n = 95)。随后,用供体皮肤(n = 25)、脑组织(n = 41)或脾细胞(n = 6)对宿主大鼠进行全身致敏,并与未致敏或假手术的同种异体移植对照组大鼠(n = 23)进行比较。所测试的任何一种致敏方法均未引发BN大鼠宿主对移植组织的排斥反应。然而,许多宿主动物中存在未导致排斥的轻微免疫反应。我们在任何一组中均未观察到W3/13 + T细胞和OX8 + 细胞毒性淋巴细胞的浸润。尽管如此,OX6 + 抗原呈递细胞和W3/25 + 辅助性T细胞出现了大量浸润。在第三脑室内发育的部分移植组织中,MHCⅠ类免疫反应性也有广泛增强,但侧脑室内相同类型的移植组织则没有这种增强。MHCⅠ类表达的增加并未伴随细胞毒性T细胞的浸润。因此,我们的研究结果表明,神经移植排斥取决于对免疫反应的一般遗传易感性,特别是实验性过敏性脑脊髓炎,而不仅仅取决于MHC编码的供体和宿主抗原之间的差异。此外,移植组织内MHCⅠ类和Ⅱ类表达的增强并不能预测移植排斥。