Cytokine and chemokine profiles in autologous graft-versus-host disease (GVM):: interleukin 10 and interferon γ may be critical mediators for the development of autologous GVHD
Cytokine and chemokine profiles in autologous graft-versus-host disease (GVM):: interleukin 10 and interferon γ may be critical mediators for the development of autologous GVHD
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DOI：
10.1182/blood-2002-01-0176
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发表时间：
2002-10-01
期刊：
影响因子：
20.3
通讯作者：
Hess, AD
中科院分区：
文献类型：
--
作者：
Miura, Y;Thoburn, CJ;Hess, AD
自体干细胞移植后使用免疫抑制药物环孢素 A (CsA) 反而会引发类似于移植物抗宿主病 (GVHD) 的全身性自身免疫综合征。这种综合征被称为自体移植物抗宿主病（autologous GVHD），与自身反应性 CD8+ T 细胞有关，这些细胞识别与恒定链肽相关的主要组织相容性复合体 (MHC) II 类决定簇。研究细胞因子和趋化因子在自体 GVHD、白细胞介素 2 (IL-2)、IL-4、IL-10、干扰素 γ (IFN-γ) 和巨噬细胞中的潜在作用 在 36 名移植后接受 CsA 治疗的患者中测定了外周血单核细胞 (PBMC) 中炎症蛋白组 (MIP-α.) 基因的表达，并与针对自体移植物的细胞溶解活性的诱导相关植物毒凝集素刺激的淋巴细胞（PHA-母细胞）和乳腺癌细胞系（T47D）。通过实时聚合酶链式反应 (PCR) 测定基因表达表明，自体 GVHD 患者的 PBMC 中 IL-10 mRNA 水平比健康个体高 29 倍。与健康个体相比，GVHD 诱发患者的 IFN-γ（4 倍）、IL-2（3 倍）和 MIP-1α（44 倍）mRNA 水平也有所增加。在自体 GVHD 期间，PBMC 裂解自体 PHA 母细胞和 T47D 肿瘤细胞的能力与 IL-10 和 IFN-γ 的表达表现出相同的时间关系。此外，在 75 名患者中评估的自体 GVHD 易感性与 IL-10(-1002) G/G 多态性等位基因、控制 IL-10 产生的启动子区域中的等位基因变异显着相关，这些发现表明 IL-10 可能在自体 GVHD 中发挥意想不到但关键的作用，并可用于增强移植后的移植物抗肿瘤效应。有趣的是，IL-10启动子区域的多态性也可以解释患者对自体GVHD诱导的易感性差异。 (C) 2002 年，美国血液学会。
Administration of the immunosuppressive drug cyclosporine A (CsA) following autologous stem cell transplantation paradoxically elicits a systemic autoimmune syndrome resembling graft-versus-host disease (GVHD). This syndrome, termed autologous GVHD, Is associated with autoreactive CD8(+) T cells that recognize major histocompatibility complex (MHC) class II determinants in association with a peptide from the Invariant chain. To Investigate the potential role of cytokines and chemokines In autologous GVHD, Interleukin 2 (IL-2), IL-4, IL-10, interferon gamma (IFN-gamma), and macrophage Inflammatory protein-lot (MIP-alpha.) gene expression In peripheral blood mononuclear cells (PBMCs) was determined In 36 patients treated with CsA following transplantation and correlated with the Induction of cytolytic activity against autologous phytolnemagglutinin-stimulated lymphocytes (PHA-blasts) and the breast cancer cell line (T47D). The determination of gene expression by real-time polymerase chain reaction (PCR) revealed that IL-10 mRNA levels by PBMCs in patients with autologous GVHD were 29-fold higher than In healthy Individuals. IFN-gamma (4-fold), IL-2 (3-fold), and MIP-1alpha (44-fold) mRNA levels were also Increased In GVHD-induced patients compared with healthy individuals. The ability of PBMCs to lyse autologous PHA-blasts and T47D tumor cells exhibited an Identical temporal relationship with expression of IL-10 and IFN-gamma during autologous GVHD. Moreover, the susceptibility to autologous GVHD as assessed In 75 patients was significantly associated with the IL-10(-1002) G/G polymorphic alleles, allelic variants In the promoter region that govern IL-10 production, These findings Indicate that IL-10 may play an unexpected but critical role In autologous GVHD and could be utilized to enhance a graft-versus-tumor effect after transplantation. Interestingly, polymorphisms In the IL-10 promoter region may also explain differences In the susceptibility of patients to autologous GVHD induction. (C) 2002 by The American Society of Hematology.