Institute of Diagnostics, School of Medicine, Shandong University, Jinan, P R China.
Mol Med. 2011 Mar-Apr;17(3-4):248-55. doi: 10.2119/molmed.2010.00133. Epub 2010 Nov 12.
Human leukocyte antigen (HLA)-G exhibits immunotolerogenicity and is related to allograft acceptance. Qa-2 is the murine homolog of HLA-G; it has structure and functions similar to those of HLA-G. We investigated the dynamic expression of Qa-2 in skin allografts by immunohistochemistry and on peripheral blood lymphocyte subsets by flow cytometry during the entire process of acute graft rejection (AGR) with a murine skin transplantation model to determine its relationship with the pathological changes of allografts and the influence of immunosuppressive therapy. In grafts without immunosuppressive treatment, Qa-2 did not exhibit obvious changes in syngeneic and allogeneic recipients. In contrast, with immunosuppressant-treated grafts, positive expression of Qa-2 was observed. It remained at high levels in the immunosuppressant-treated syngeneic group; however, it became weakly positive and even negative in infiltrating inflammatory cells as AGR advanced, but it remained strongly positive in other skin tissues throughout the AGR process. Qa-2 expression on CD4(+) and CD8(+) peripheral blood lymphocyte subsets remained stable at a normal level in the non-immunosuppressant-treated syngeneic group. Immunosuppressive treatment can also significantly upregulate Qa-2. In the allogeneic groups, decreased expression was observed when AGR was at histological grades 1 to 2 (well before gross rejection was observed). Qa-2 was upregulated again after the graft was rejected completely. The results suggest that the increase in Qa-2 may be attributed to the use of immunosuppressive treatments. Moreover, Qa-2 expression decreased significantly with AGR progression, suggesting that it may be a potential marker for predicting AGR, especially in the presence of immunosuppressive agents.
人类白细胞抗原 (HLA)-G 具有免疫耐受特性,与同种异体移植物的接受有关。Qa-2 是 HLA-G 的鼠类同源物;它具有与 HLA-G 相似的结构和功能。我们通过免疫组织化学技术检测了 Qa-2 在皮肤同种异体移植物中的动态表达,并通过流式细胞术检测了外周血淋巴细胞亚群,以研究其在急性移植物排斥反应(AGR)过程中的变化,从而确定其与移植物病理变化的关系以及免疫抑制治疗的影响。在未接受免疫抑制治疗的移植物中,同种和异体受者的 Qa-2 没有明显变化。相反,在接受免疫抑制治疗的移植物中,观察到 Qa-2 的阳性表达。在接受免疫抑制治疗的同基因组中,其表达水平保持较高;然而,随着 AGR 的进展,浸润性炎症细胞中的 Qa-2 表达逐渐减弱甚至阴性,但在整个 AGR 过程中,其他皮肤组织中仍保持强阳性。在未接受免疫抑制治疗的同基因组中,CD4(+)和 CD8(+)外周血淋巴细胞亚群的 Qa-2 表达保持在正常水平。免疫抑制治疗也可显著上调 Qa-2。在同种异体组中,当 AGR 处于组织学 1 至 2 级(在明显排斥之前)时,其表达量降低。当移植物完全排斥后,Qa-2 再次上调。结果表明,Qa-2 的增加可能归因于免疫抑制治疗的应用。此外,随着 AGR 的进展,Qa-2 的表达显著降低,这表明它可能是预测 AGR 的一个潜在标志物,尤其是在存在免疫抑制剂的情况下。