Department of Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.
Transpl Immunol. 2011 Jan 15;24(2):113-8. doi: 10.1016/j.trim.2010.10.005. Epub 2010 Oct 16.
IFN-γ was documented to be commonly associated with acute rejection. In the present study, we investigated the role of IFN-γ in the transplant long-surviving induced by blocking CD40-CD40 ligand (CD40-CD40L) costimulation and its mechanisms.
IFN-γ expression in cardiac allografts and spleens from syngeneic and allogeneic recipients with or without anti-CD40L monoclonal antibody (MR-1) treatment was examined by real-time RT-PCR. The grafts survival time in Wild type (IFN-γ(+/+)) and IFN-γ deficient (IFN-γ(-/-)) recipients was investigated. Mixed lymphocyte reaction (MLR) of CD4(+) T cells and cytotoxic T lymphocyte (CTL) assay of CD8(+) T cells were also studied. FoxP3 expression in allografts and spleens from IFN-γ(+/+) or IFN-γ(-/-) recipients with MR-1 treatment was examined. Furthermore, FoxP3, IL-10 and CTLA-4 expressions and the suppressive capability of CD4(+)CD25(+) regulatory T cells were examined.
Rejected allografts showed significantly higher IFN-γ expression than long-surviving allografts. Allograft survival was not prolonged in nonimmunosuppressed IFN-γ(-/-) mice. Administration of MR-1 induced long-term survival in 90.1% of IFN-γ(+/+) recipients (98±6.6 days) but failed to do so in IFN-γ(-/-) group (16.2±4.0 days). IFN-γ(-/-) recipients facilitated the proliferation and CTL generation of T cells. The allografts and spleens from IFN-γ(+/+) recipients contained higher FoxP3 expression than IFN-γ(-/-) recipients. Moreover, CD4(+)CD25(+) T cells from IFN-γ(+/+) recipients displayed a higher FoxP3 and IL-10 expression and suppressive capability.
IFN-γ plays an important role in the long-surviving induced by blocking CD40-CD40L through inhibiting the function of activated T cells and increasing suppressive capability of CD4(+)CD25(+) regulatory T cells.
IFN-γ 通常与急性排斥反应有关。在本研究中，我们研究了阻断 CD40-CD40L 共刺激对 IFN-γ 在移植长期存活中的作用及其机制。
通过实时 RT-PCR 检测同基因和同种异体受体心脏移植物和脾脏中 IFN-γ 的表达，以及是否用抗 CD40L 单克隆抗体（MR-1）治疗。在野生型（IFN-γ(+/+)）和 IFN-γ 缺陷型（IFN-γ(-/-)）受体中研究移植物的存活时间。还研究了 CD4(+)T 细胞的混合淋巴细胞反应（MLR）和 CD8(+)T 细胞的细胞毒性 T 淋巴细胞（CTL）测定。用 MR-1 治疗后，观察 IFN-γ(+/+)或 IFN-γ(-/-)受体中移植物和脾脏中 FoxP3 的表达，并检查 FoxP3、IL-10 和 CTLA-4 的表达以及 CD4(+)CD25(+)调节性 T 细胞的抑制能力。
排斥的同种异体移植物显示出明显高于长期存活的同种异体移植物的 IFN-γ 表达。在未免疫抑制的 IFN-γ(-/-)小鼠中，同种异体移植物的存活时间没有延长。MR-1 的给药诱导 90.1%的 IFN-γ(+/+)受体的长期存活（98±6.6 天），但在 IFN-γ(-/-)组中不能（16.2±4.0 天）。IFN-γ(-/-)受体促进 T 细胞的增殖和 CTL 生成。IFN-γ(+/+)受体的同种异体移植物和脾脏中的 FoxP3 表达高于 IFN-γ(-/-)受体。此外，IFN-γ(+/+)受体的 CD4(+)CD25(+)T 细胞表现出更高的 FoxP3 和 IL-10 表达和抑制能力。
IFN-γ 通过抑制活化 T 细胞的功能和增加 CD4(+)CD25(+)调节性 T 细胞的抑制能力，在阻断 CD40-CD40L 诱导的长期存活中发挥重要作用。
