Ma N, Streilein J W
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Invest Ophthalmol Vis Sci. 1998 Nov;39(12):2384-93.
To determine whether donor-derived microglial cells play a role in dictating the immunogenicity of immature neuronal retinal tissue transplanted intraocularly.
Neonatal neural retinas (aged <24 hours) from C57BL/6 or BALB/c mice were implanted in the anterior chamber or the subretinal space of adult syngeneic or allogeneic eyes. After 12 and 35 days of engraftment, retinal grafts were harvested and analyzed immunohistochemically with 20 microg/ml Griffonia simplicifolia (GS) isolectin to identify microglia and define their morphology, monoclonal antibodies to study expression of donor and recipient major histocompatibility complex (MHC) class I and II antigens, and anti-CD3 and -CD14 antibodies to distinguish microglia from T cells and macrophages.
Neonatal retinas were found to contain significant numbers of GS+ cells (microglia) at the time of grafting. By day 12 after grafting, markedly increased numbers of microglia were found in syngeneic and allogeneic grafts. Whereas most microglia in syngeneic grafts displayed a ramified (inactive) morphology at this time, most of the microglia in allografts displayed an ameboid (activated) configuration, with retracted processes and enlarged somas. By day 35 after grafting, although the density of microglia was reduced in syngeneic and allogeneic grafts, intensely labeled GS+ cells were localized in the centers of rosettes in syngeneic, but not in allogeneic, grafts. Instead, donor-derived microglia displayed intense expression of MHC class I and II antigens, and these grafts contained small numbers of recipient-derived T cells, but not macrophages.
Microglia within developing neuronal retinal transplants display morphologic features that are consistent with the ability to function as "passenger leukocytes," and they distribute themselves within rosettes as though performing surrogate support functions usually adopted by retinal pigment epithelial cells. Because this latter property causes activation of the microglia, it may also cause these cells to enhance the immunogenicity of the allograft.
确定供体来源的小胶质细胞在决定眼内移植的未成熟神经元视网膜组织的免疫原性方面是否起作用。
将来自C57BL/6或BALB/c小鼠的新生神经视网膜（年龄<24小时）植入成年同基因或异基因眼的前房或视网膜下间隙。移植12天和35天后，收获视网膜移植物，并用20微克/毫升的西非豆科凝集素（GS）同工凝集素进行免疫组织化学分析，以鉴定小胶质细胞并确定其形态，用单克隆抗体研究供体和受体主要组织相容性复合体（MHC）I类和II类抗原的表达，并用抗CD3和抗CD14抗体将小胶质细胞与T细胞和巨噬细胞区分开来。
发现新生视网膜在移植时含有大量GS+细胞（小胶质细胞）。移植后第12天，在同基因和异基因移植物中发现小胶质细胞数量明显增加。此时，同基因移植物中的大多数小胶质细胞呈现分支状（无活性）形态，而异基因移植物中的大多数小胶质细胞呈现阿米巴样（活化）形态，突起回缩，胞体增大。移植后第35天，尽管同基因和异基因移植物中小胶质细胞的密度降低，但强烈标记的GS+细胞位于同基因移植物而非异基因移植物的玫瑰花结中心。相反，供体来源的小胶质细胞呈现MHC I类和II类抗原的强烈表达，并且这些移植物含有少量受体来源的T细胞，但不含巨噬细胞。
发育中的神经元视网膜移植中的小胶质细胞表现出与作为“过客白细胞”发挥功能的能力相一致的形态特征，并且它们在玫瑰花结内分布，就好像在执行通常由视网膜色素上皮细胞承担的替代支持功能。由于后一种特性会导致小胶质细胞活化，它也可能导致这些细胞增强同种异体移植物的免疫原性。
