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IFN-γ Control of an Effector/Target Combination for Skin Allograft Rejection: Macrophage/Skin Components in Normal Mice or T Cell/Endothelial Cells in IFN-γ-Deficient Mice.
Journal of Interferon & Cytokine Research ( IF 1.9 ) Pub Date : 2020-02-18 , DOI: 10.1089/jir.2019.0129
Ryotaro Yoshida 1 , Shogo Maeda 1 , Junko Tashiro-Yamaji 1 , Emi Yasuda 2 , Yuro Shibayama 2 , Yoshinobu Hirose 2 , Takahiro Kubota 1
Affiliation  

Organ, skin, or cell allografts are acutely rejected from normal mice, whereas vascularized organ allografts, but not allografted Meth A cells, are rejected from interferon-γ (IFN-γ)-deficient mice. Here we explored effector/target combinations for i.p. allografted Meth A (cytotoxic T lymphocyte [CTL]-resistant) or RLmale1 (CTL-susceptible) cells into or for BALB/c skin (skin components: CTL resistant) onto normal or IFN-γ-deficient C57BL/6 mice. After allografting, normal mice showed more infiltration but only a little thrombosis/hemorrhage. Monocyte/macrophage MHC receptor (MMR)+ macrophages (on days 5-10) and T cell receptor (TCR)+ CTLs (on days 7-9) were cytotoxic against Meth A cells or skin components and RLmale1 cells, respectively, and the allografts were rejected. After allografting into IFN-γ-deficient mice, MMR- macrophages and highly activated TCR+ CTLs were induced, and the mice died of hemorrhagic ascites with Meth A cells and more acutely rejected RLmale1 cells. The CTLs on days 4-6 were inactive toward skin components at an in vivo effector/target ratio but injured endothelial cells to cause severe thrombosis/hemorrhage and more acute rejection of skin allografts. These results indicate that IFN-γ-dependent MMR expression was essential for macrophage-mediated cytolysis of allogeneic skin components and that IFN-γ-deficient mice more acutely rejected skin allograft by causing CTL-induced injury to endothelial cells.

中文翻译:

用于皮肤同种异体移植排斥的效应器/靶标组合的 IFN-γ 控制:正常小鼠中的巨噬细胞/皮肤成分或 IFN-γ 缺陷小鼠中的 T 细胞/内皮细胞。

器官、皮肤或细胞同种异体移植物会被正常小鼠急性排斥,而血管化器官同种异体移植物,而不是同种异体移植的 Meth A 细胞,会被干扰素-γ (IFN-γ) 缺陷小鼠排斥。在这里,我们探索了 ip 同种异体移植 Meth A(细胞毒性 T 淋巴细胞 [CTL] 抗性)或 RLmale1(CTL 易感)细胞进入或用于 BALB/c 皮肤(皮肤成分:CTL 抗性)到正常或 IFN-γ 的效应子/靶点组合- 缺陷的 C57BL/6 小鼠。同种异体移植后,正常小鼠表现出更多浸润,但只有少量血栓形成/出血。单核细胞/巨噬细胞 MHC 受体 (MMR)+ 巨噬细胞(第 5-10 天)和 T 细胞受体(TCR)+ CTL(第 7-9 天)分别对 Meth A 细胞或皮肤成分和 RLmale1 细胞具有细胞毒性,并且同种异体移植被拒绝。在同种异体移植到 IFN-γ 缺陷小鼠中后,MMR-巨噬细胞和高度活化的 TCR+ CTL 被诱导,小鼠死于出血性腹水,并伴有 Meth A 细胞和更急性排斥的 RLmale1 细胞。第 4-6 天的 CTL 在体内效应物/靶标比率下对皮肤成分无活性,但会损伤内皮细胞,导致严重的血栓形成/出血和更严重的同种异体皮肤排斥。这些结果表明,依赖于 IFN-γ 的 MMR 表达对于巨噬细胞介导的同种异体皮肤成分的细胞溶解是必不可少的,并且 IFN-γ 缺陷小鼠通过引起 CTL 诱导的内皮细胞损伤更严重地排斥同种异体皮肤移植物。第 4-6 天的 CTL 在体内效应物/靶标比率下对皮肤成分无活性,但会损伤内皮细胞,导致严重的血栓形成/出血和更严重的同种异体皮肤排斥。这些结果表明,依赖于 IFN-γ 的 MMR 表达对于巨噬细胞介导的同种异体皮肤成分的细胞溶解是必不可少的,并且 IFN-γ 缺陷小鼠通过引起 CTL 诱导的内皮细胞损伤更严重地排斥同种异体皮肤移植物。第 4-6 天的 CTL 在体内效应物/靶标比率下对皮肤成分无活性,但会损伤内皮细胞,导致严重的血栓形成/出血和更严重的同种异体皮肤排斥。这些结果表明,依赖于 IFN-γ 的 MMR 表达对于巨噬细胞介导的同种异体皮肤成分的细胞溶解是必不可少的,并且 IFN-γ 缺陷小鼠通过引起 CTL 诱导的内皮细胞损伤更严重地排斥同种异体皮肤移植物。
更新日期:2020-02-18
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