Jiang L Q, Jorquera M, Streilein J W, Ishioka M
Schepens Eye Research Institute, Boston, Massachusetts 02114, USA.
Transplantation. 1995 Apr 27;59(8):1201-7.
The unique feature of neural transplantation in the central nervous system is that the graft is derived from and implanted into an immunologically privileged site. The eye, as a part of the central nervous system, normally maintains an immunosuppressive microenvironment in which alloantigens induce an active down-regulation of specific delayed hypersensitivity. To determine whether neural retinal allografts are eventually rejected and, if so, what type of immunity is associated with rejection, we implanted allogeneic and syngeneic newborn neural retinal grafts into the anterior chamber of the eyes of immune-competent mice. In addition, similar allografts were implanted into severe combined immune-deficient (SCID) mice. The fate of these grafts was determined by clinical and histological examination. At post-implantation day 12, all allogeneic and syngeneic grafts survived comparably well with no evidence of inflammation. At post-implantation day 35, the syngeneic grafts in the immune-competent mice and the allogeneic grafts in the SCID mice continued to thrive, whereas the allografts in the immune-competent mice were remarkably reduced in size and had lost the organization of their retinal cell layers. Interestingly, these grafts' deterioration occurred with no obvious cellular infiltration. When systemic graft-specific immunity was examined, it was found that delayed hypersensitivity was impaired at post-implantation day 12 in allograft recipients. However, by post-implantation 35 day when deterioration was detected in these grafts, suppression of immunity was replaced by vigorous delayed hypersensitivity. These results suggest that intraocular retinal allografts eventually succumb to rejection and that rejection is correlated with the emergence of donor-specific delayed hypersensitivity. The possible relationships of atypical, chronic rejection of intraocular neural retinal allografts to emergent delayed hypersensitivity are discussed.
中枢神经系统神经移植的独特之处在于移植组织源自并植入免疫赦免部位。眼睛作为中枢神经系统的一部分,通常维持着一种免疫抑制微环境,同种异体抗原在其中会诱导特异性迟发型超敏反应的主动下调。为了确定神经视网膜同种异体移植最终是否会被排斥,如果会,与排斥相关的是何种免疫类型,我们将同种异体和同基因新生神经视网膜移植到有免疫活性小鼠的眼前房。此外,将类似的同种异体移植植入严重联合免疫缺陷(SCID)小鼠体内。通过临床和组织学检查确定这些移植组织的命运。植入后第12天,所有同种异体和同基因移植组织存活情况相当良好,无炎症迹象。植入后第35天,有免疫活性小鼠体内的同基因移植组织和SCID小鼠体内的同种异体移植组织继续生长,而有免疫活性小鼠体内的同种异体移植组织大小显著减小,视网膜细胞层结构丧失。有趣的是,这些移植组织的退化没有明显的细胞浸润。当检测全身移植特异性免疫时,发现同种异体移植受体在植入后第12天迟发型超敏反应受损。然而,到植入后第35天这些移植组织出现退化时,免疫抑制被强烈的迟发型超敏反应所取代。这些结果表明眼内视网膜同种异体移植最终会因排斥而失败,且排斥与供体特异性迟发型超敏反应的出现相关。本文讨论了眼内神经视网膜同种异体移植非典型慢性排斥与迟发型超敏反应出现之间的可能关系。