Theele D P, Schrimsher G W, Reier P J
Division of Comparative Medicine, College of Veterinary Medicine, University of Florida, Gainesville 32610, USA.
Exp Neurol. 1996 Nov;142(1):128-43. doi: 10.1006/exnr.1996.0184.
Most studies investigating early fetal CNS graft-host interactions and host immune responses have been performed using intracerebral transplantation paradigms. The purpose of this study was to establish the early developmental dynamics of fetal graft integration with the injured host spinal cord and to determine whether fetal allografts in this environment are subject to rejection. ACI rat fetal spinal cord (FSC) tissue was grafted into acute lesion cavities of adult WF rat spinal cords. Graft development and/or rejection was followed from 1 to 45 days posttransplantation with morphometric, histological, and immunocytochemical methods. We determined that all FSC grafts in acute resection lesions of the adult rat spinal cord undergo an early substantial cellular attrition, but following favorable attachment to healthy host tissue margins, they rebound and grow to fill the lesion cavity by approximately 45 days. We also determined that FSC allografts into nonimmunosuppressed adult recipients are consistently rejected, but only after an early period of growth and maturation. The onset of rejection is characterized by extensive cellular infiltration coincidental with graft and host MHC antigen expression. The implications of delayed graft development and graft-host integration are discussed relative to interconnectivity and long-term potential for graft-derived benefits. The observed rejection response was characteristic of first-order allograft rejection and underscores a lack of immunological privilege in the microenvironment of the injured spinal cord.
大多数研究早期胎儿中枢神经系统移植物与宿主相互作用及宿主免疫反应的实验都是采用脑内移植模式进行的。本研究的目的是确定胎儿移植物与受损宿主脊髓整合的早期发育动态,并确定在这种环境下胎儿同种异体移植物是否会被排斥。将ACI大鼠胎儿脊髓(FSC)组织移植到成年WF大鼠脊髓的急性损伤腔内。在移植后1至45天,采用形态计量学、组织学和免疫细胞化学方法跟踪移植物的发育和/或排斥情况。我们确定,成年大鼠脊髓急性切除损伤中的所有FSC移植物在早期都会经历大量细胞损耗,但在与健康宿主组织边缘良好附着后,它们会反弹并在大约45天时生长以填充损伤腔。我们还确定,植入未免疫抑制成年受体的FSC同种异体移植物始终会被排斥,但仅在早期生长和成熟之后。排斥反应的开始表现为广泛的细胞浸润,同时伴有移植物和宿主MHC抗原表达。相对于移植物的互连性和长期潜在益处,讨论了移植物发育延迟和移植物 - 宿主整合的影响。观察到的排斥反应是一级同种异体移植排斥反应的特征,强调了受损脊髓微环境中缺乏免疫豁免权。