Purpose: To investigate immunological differences and the role of CD38+/F4/80 + M1 macrophages in C57BL/6J- and BALB/c-recipient mouse corneal transplantation models. Methods: Allogeneic transplantation was performed crosswise in BALB/c mice and C57BL/6J mice; syngeneic transplantation was performed in both strains. Anterior chamber depth (ACD) was measured before and central corneal thickness (CCT) was measured both before and after transplantation. In vivo graft rejection was monitored using anterior eye segment optical coherence tomography (ASOCT) evaluating the CCT and grading of corneal oedema using a well-established clinical score (CS). Histology of corneal grafts was performed 18 or 21 days after surgery. Immunohistochemistry with anti-F4/80 antibody and anti-CD38 antibody was used for detecting M1 macrophages within the grafts. Results: High CS and CCT values after allogeneic transplantation persisted in both BALB/c (n = 18) and C57BL/6J recipients (n = 20). After syngeneic transplantation, CS and CCT values increased in both models in the early phase after surgery due to the surgical trauma. Surprisingly, in the syngeneic C57BL/6J model, high CCT values persisted. Furthermore, anterior synechiae developed in C57BL/6 recipients after both syngeneic and allogeneic transplantation, whereas BALB/c recipients showed almost no synechiae – even though C57/BL6J animals tended to have a deeper anterior chamber (281 ± 11 pixels [mean ± SD]) compared with BALB/c animals of the same age (270 ± 9 pixels [mean ± SD]). Immunohistochemistry revealed numerous CD38+/F4/80 + M1 macrophages in grafts of C57BL/6J recipients following both syngeneic and allogeneic transplantation. However, in BALB/c-recipient mice only sparse M1 macrophages were detectable (CD38 + M1 macrophages relative to all F4/80 + cells: 75 vs. 17% [after allogeneic transplantation] and 66 vs. 17% [after syngeneic transplantation]; p #x3c; 0.05). Conclusions: Allogeneic corneal transplants are rejected in BALB/c as well as C57BL/6J mice, but tissue alterations with anterior synechiae are more pronounced in C57BL/6J recipients. Following syngeneic transplantation, C57BL/6J-recipient animals show a persistent graft swelling with increased numbers of CD38+/F4/80 + M1 macrophages in grafted tissue, in contrast to the common model using BALB/c-recipient mice. Our data strongly suggest that strain-dependent differences convey different innate immune responses in BALB/c and C57BL/6J strains. Accordingly, in murine keratoplasty experiments, the mouse line of both donor and recipient animals must be carefully considered. C57BL/6J-recipient mice might be particularly suited to study corneal graft rejection in a clinical setting considered “high risk.”
J Innate Immun

中文翻译：

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角膜移植后 BALB/c 和 C57BL/6 菌株的不同先天免疫反应。

目的：研究CD38+/F4/80+M1巨噬细胞在C57BL/6J-和BALB/c-受体小鼠角膜移植模型中的免疫学差异和作用。方法：在BALB/c小鼠和C57BL/6J小鼠中交叉进行同种异体移植；两种菌株均进行了同基因移植。前房深度（ACD）在移植前测量，中央角膜厚度（CCT）在移植前后测量。使用眼前段光学相干断层扫描 (ASOCT) 监测体内移植物排斥反应，使用完善的临床评分 (CS) 评估 CCT 和角膜水肿分级。角膜移植物的组织学在手术后 18 或 21 天进行。使用抗 F4/80 抗体和抗 CD38 抗体的免疫组织化学检测移植物中的 M1 巨噬细胞。结果：同种异体移植后高 CS 和 CCT 值在 BALB/c ( n= 18) 和 C57BL/6J 接受者 ( n= 20）。同基因移植后，由于手术创伤，两种模型在手术后早期的 CS 和 CCT 值均增加。令人惊讶的是，在同基因 C57BL/6J 模型中，高 CCT 值持续存在。此外，在同基因和同种异体移植后，C57BL/6 受者出现前房粘连，而 BALB/c 受者几乎没有出现粘连——尽管 C57/BL6J 动物往往有更深的前房（281±11 个像素 [平均值±SD]） ) 与同龄 BALB/c 动物相比 (270 ± 9 像素 [平均值 ± SD])。免疫组织化学显示，在同种和同种异体移植后，C57BL/6J 受者的移植物中存在大量 CD38+/F4/80+M1 巨噬细胞。然而，在 BALB/c 受体小鼠中，仅可检测到稀疏的 M1 巨噬细胞（CD38 + M1 巨噬细胞相对于所有 F4/80 + 细胞：p #x3c; 0.05）。结论：同种异体角膜移植在 BALB/c 和 C57BL/6J 小鼠中被排斥，但在 C57BL/6J 受体中，前粘连的组织改变更为明显。同基因移植后，C57BL/6J 受体动物表现出持续的移植肿胀，移植组织中 CD38+/F4/80 + M1 巨噬细胞数量增加，这与使用 BALB/c 受体小鼠的常见模型形成对比。我们的数据强烈表明，菌株依赖性差异在 BALB/c 和 C57BL/6J 菌株中传达了不同的先天免疫反应。因此，在小鼠角膜移植术实验中，必须仔细考虑供体和受体动物的小鼠线。C57BL/6J 受体小鼠可能特别适合在被认为是“高风险”的临床环境中研究角膜移植排斥反应。
J先天免疫