Clément M V, Soulié A, Legros-Maida S, Guillet J, Gluckman E, Sigaux N, Sasportes M
Unité de greffe de moëlle, Hôpital Saint-Louis, Paris, France.
Nouv Rev Fr Hematol (1978). 1991;33(6):465-70.
Monitoring of human allografts requires to use histological, immunohistochemical and functional techniques to characterize graft infiltrating cells. Granzyme B and perforin gene expression is of major importance in functional studies. Those proteins are present in the cytoplasmic granules of cytotoxic T lymphocytes and are secreted during granule exocytosis at the effector/target cell interface. Gene expression of both proteins has been studied by in situ hybridization using specific riboprobes on serial sections of biopsies in two pathological models. Our results show that cells infiltrating early skin lesions of patients with acute GVHD after bone marrow graft are exclusively composed of T cells, among which some of them express granzyme B and perforin genes. Similarly the presence of granzyme B and perforine-expressing cells in endomyocardial biopsies of heart transplanted patients has been associated to early and severe crisis of rejection. In contrast, the absence of functional markers in lymphoid infiltrates was coinciding with less aggressive and late episodes of rejection. Taken together, our data indicate that granzyme B and perforin gene expression in skin infiltrating lymphocytes during GVH or within heart infiltrating cells during crisis of rejection are in favor of severe processes. The study has allowed to predict during heart transplantation the apparition of a rejection crisis and to show the necessity for treating the patient with immunsuppresive drugs. This is also the case for patients with GVHD at the time of the first skin rash.
对人类同种异体移植的监测需要使用组织学、免疫组织化学和功能技术来鉴定移植物浸润细胞。颗粒酶B和穿孔素基因表达在功能研究中至关重要。这些蛋白质存在于细胞毒性T淋巴细胞的细胞质颗粒中，并在效应细胞/靶细胞界面的颗粒胞吐过程中分泌。在两种病理模型中，通过使用特异性核糖探针在活检连续切片上进行原位杂交来研究这两种蛋白质的基因表达。我们的结果表明，骨髓移植后急性移植物抗宿主病患者早期皮肤病变中的浸润细胞仅由T细胞组成，其中一些细胞表达颗粒酶B和穿孔素基因。同样，心脏移植患者心内膜活检中存在表达颗粒酶B和穿孔素的细胞与早期严重排斥反应相关。相反，淋巴浸润中缺乏功能标志物与侵袭性较小的晚期排斥反应发作同时出现。综上所述，我们的数据表明，移植物抗宿主病期间皮肤浸润淋巴细胞或排斥反应期间心脏浸润细胞中颗粒酶B和穿孔素基因表达有利于严重病程。该研究能够在心脏移植期间预测排斥反应危机的出现，并表明对患者使用免疫抑制药物治疗的必要性。首次出现皮疹时患有移植物抗宿主病的患者也是如此。
