造血干细胞移植后免疫状态的研究进展

造血干细胞移植后面临的重要问题是移植后感染和肿瘤复发，移植后免疫重建迟于造血重建，甚至两年后免疫功能仍有缺陷，因此移植后免疫状态的研究对于指导免疫重建、防治感染及免疫治疗等有重要意义。本文就移植后免疫细胞的数量、功能变化及其机制作一综述。     

造血干细胞移植后免疫状态的研究进展

造血干细胞移植后面临的重要问题是移植后感染和肿瘤复发 ,移植后免疫重建迟于造血重建 ,甚至两年后免疫功能仍有缺陷 ,因此移植后免疫状态的研究对于指导免疫重建、防治感染及免疫治疗等有重要意义。本文就移植后免疫细胞的数量、功能变化及其机制作一综述     

造血干细胞移植治疗自身免疫性疾病

自从1995年造血干细胞移植（HSCT）应用于难治复发性自身免疫性疾病（AID）的治疗以来,取得了令人鼓舞的疗效,最近已经进入Ⅲ期临床试验阶段。AID可能是一种造血干细胞异常所致疾病,本文主要就自体或异体HSCT治疗AID的原理及自体HSCT治疗几种主要AID的临床试验结果做一综述。     

030 造血干细胞移植后免疫状态的研究进展

造血干细胞移植后面临的重要问题是移植后感染和肿瘤复发，移植后免疫重建迟于造血重建，甚至两年后免疫功能仍有缺陷，因此移植后免疫状态的研究对于指导免疫重建、防治感染及免疫治疗等有重要意义。本文就移植后免疫细胞的数量、功能变化及其机制作一综述。     

造血干细胞移植后免疫重建

造血干细胞移植（HSCT）已广泛应用于临床,是治疗血液系统疾患、实体瘤、基因缺陷及自身免疫性疾病的重要手段干细胞移植伴随着严重的免疫缺陷,这一时期,患者有合并严重感染的风险固有免疫恢复迅速．NK细胞、树突状细胞移植后数周内即可恢复。而适应性免疫系统恢复缓慢,T细胞和B细胞移植后数月才可恢复正常,而T细胞功能恢复需要数年的时间：研究造血系统各细胞存移植后数量、功能上的恢复规律,对如何加快免疫重建,降低移植死亡率有重要意义.     

造血干细胞移植临床治疗进展

造血干细胞移植 (HSCT)是近 2 0多年发展起来的医疗技术 ,与众多的基础科学相关。在我国 ,由于每年约有 3～ 4万人患上白血病 ,而希望通过移植来根治该病的理论学说和实际临床操作尚存在许多待研究的问题。主要表现在 HSCT后 ,疾病转变无法准确预测 ,影响因素复杂 ,包括对机体产生的正、负影响的双重效应。在这种利弊共存的体内环境中 ,有效控制 HSCT之后产生的危害性 ,对提高机体抗疾病的免疫能力具有极重要的临床意义。本文拟综述从细胞和分子水平分析造血干细胞成分与受体免疫系统之间的免疫反应。1　免疫耐受性作用移植物抗宿主疾…     

异基因造血干细胞移植后免疫功能重建

异基因造血干细胞移植(allo-HSCT)后患者的免疫功能受到严重损伤,移植后免疫功能低下主要表现在①免疫个体发生学过程再现的削弱;②缺乏长期稳定的供体免疫功能的转移;③移植物抗宿主病(GVHD)对免疫功能的影响;④胸腺功能的降低.临床实践证实,清髓性治疗后患者的免疫功能处于麻痹状态可以持续1年之久.     

异基因造血干细胞移植后骨髓免疫微环境重建研究

GVHD 和GVL 是影响异基因造血干细胞移植术成败的关键因素。骨髓不仅是造血器官,更是免疫器官,骨髓中的免疫微环境关乎移植后造血重建、免疫功能重建、移植后白血病复发。本文将从骨髓微环境的病理生理特点、异基因造血干细胞移植后免疫功能重建、骨髓免疫微环境与移植后造血恢复及移植后白血病复发等角度,综述近年来关于异基因造血干细胞移植后骨髓免疫微环境重建与造血重建和白血病复发相关研究情况。     

造血干细胞移植与自身免疫病

自身免疫与免疫耐受是当今免疫学研究的中心课题。随着免疫应答,免疫耐受机理被逐步揭示,自身免疫病的治疗越来越受到研究者及临床医生的关注。近年的研究表明造血干细胞的异常是导致自身免疫疾病的发生的根本原因,其中很多自身免疫病已在基因水平找到了相应的缺陷。本文拟从动物实验及临床治疗两方面对用造血干细胞移植治疗自身免疫病的研究与应用作一综述。     

同基因造血干细胞移植免疫重建诱导小鼠皮肤移植耐受

背景：器官移植耐受的最佳效果是能够诱导对移植抗原的特异性免疫耐受。 目的：探讨小鼠异基因皮肤移植后,通过受体同基因造血干细胞移植重建免疫系统诱导移植皮肤免疫耐受的可行性。 方法：取BALB/c小鼠骨髓。以C57BL/6小鼠为供体,BALB/c小鼠为受体,进行异基因皮肤移植;32只受体鼠随机均分为4组：移植对照组、环孢素A组、照射组和骨髓移植组。 结果与结论：照射组小鼠10 d内全部死亡,外周血白细胞数呈持续性降低;而骨髓移植组小鼠长期存活,白细胞数全身照射后6 d降到最低,之后持续性增高,照射后21 d与环孢素A组比较差异无显著性意义(P > 0.05),移植皮肤存活时间显著长于其他各组(P < 0.01),其淋巴细胞浸润及组织结构破坏明显减少,小鼠脾细胞对供体小鼠脾细胞增殖反应显著降低。说明同基因骨髓细胞移植重建免疫系统可显著延长小鼠移植皮肤存活时间,可诱导供者特异性免疫耐受。     

Immunological aspects of pancreatic islet cell transplantation

Type 1 diabetes mellitus (T1DM) is one of the most common diseases of childhood. Insulin discovery changed the clinical course of T1DM from an acutely fatal disease to a chronic disease, but this discovery was later found to be inefficient to control its long-term complications. Whole-pancreas and islet cell transplantation seem to provide a potential solution by restoring the normal physiology of glucose–insulin homeostasis. Although islet transplantation is less invasive than whole-pancreas transplantation, the insulin-free state after islet transplantation remained low (10%) at 5 years after surgery. Here, we will present the specific immunologic challenges that are specific to islet cell transplantation, including instant blood-mediated inflammatory reaction and the recurrence of autoimmunity. We will also briefly discuss the immunosuppressive regimens used and the recent radiologic techniques in the detection of engraftment and early rejection of islet cells.     

Immunological basis of stem cell therapy in liver diseases

Unbalanced immune cell populations or immune cell infiltration of the liver can disrupt the immune-privileged state of the liver, resulting in liver injury or fibrosis. Therefore, the treatment for liver diseases involves not only hepatic regeneration but also immunological regulation. Recent studies demonstrated that stem cells, especially mesenchymal stem cells, have the capacity for not only hepatic differentiation but also immunomodulation. In this respect, stem cell therapy could be a realistic aim for liver diseases by modulating the liver regenerative processes and down-regulating immune-mediated liver damage. In this review, we discuss in detail the importance of immune cells in liver injury and repair; the mechanism by which stem cells demonstrate an immune-tolerant phenotype that can be used for allogeneic transplantation; the effect of stem cell transplantation on immune-mediated diseases, especially liver diseases; and the mechanism by which stem cells improve the hepatic microenvironment.     

Hematopoietic stem cell transplantation procedures

Hematopoietic stem cell transplantation has been utilized for the treatment of severe autoimmune diseases following the results of experimental studies and of coincidental diseases. While allogeneic transplantation is still being explored, autologous transplantation is the procedure most frequently utilized worldwide. The rationale for its utilization consists in its powerful immunosuppressive effect, but immune modulation polarized towards tolerance is also postulated. The mobilization of stem and progenitor cells from the marrow and the various conditioning regimens derive from the experience with hematologic malignancies. The greatest possible reduction of transplant-related-mortality and of the autoimmune aggression are being actively pursued. Here, the main procedural modalities will be analyzed and discussed.     

Hematopoietic stem cell transplantation procedures

Hematopoietic stem cell transplantation has been utilized for the treatment of severe autoimmune diseases following the results of experimental studies and of coincidental diseases. While allogeneic transplantation is still being explored, autologous transplantation is the procedure most frequently utilized worldwide. The rationale for its utilization consists in its powerful immunosoppressive effect, but immune modulation polarized towards tolerance is also postulated.

The mobilization of stem and progenitor cells from the marrow and the various conditioning regimens derive from the experience with hematologic malignancies. The greatest possible reduction of trasplant-related-mortality and of the autoimmune aggression are being actively pursued. Here, the main procedural modalities will be analyzed and discussed.     

Allogenic stem cell transplantation after non-myeloablative conditioning regimen (mini-allogenic" stem cell transplantation)

Allogeneic stem cell transplantation is able to cure many hematologic malignancies, through, at least partially, a graft versus disease effect of the donor's immune system transfer. However, the toxicity of this technique limits its use to selected patients. The aim of non-myeloablative stem cell transplantation is to reduce the toxicity of the conditioning regimen while allowing the engrafement of donor's stem cells and the immunological antitumoral activity of the donor's immune system. Several reports have already demonstrated the validity of this concept. This new multi-step therapeutic strategy is complex, raises many questions and deserves further studies to be fully applicable to a greater number of patients.     

Red cell transfusion thresholds in haematopoietic stem cell transplantation

Red cell transfusions are part of the routine supportive care following haematopoietic stem cell transplantation. There is increasing evidence from randomized controlled trials demonstrating that restrictive transfusion thresholds are equivalent to liberal thresholds in other patient populations. However, given the lack of patient‐centred outcomes and the longer transfusion support required for patients with haematologic malignancies, the results of these trials may not be generalizable to haematology–oncology patients. In the recently completed multicentre TRIST trial, we randomized 300 patients requiring an autologous or allogeneic haematopoietic stem cell transplantation to either a restrictive (haemoglobin threshold <70 g/l) or liberal (haemoglobin threshold <90 g/l) red cell transfusion strategy. Our primary outcome was health‐related quality of life measured by FACT‐BMT through day 100 post‐transplant. The median number of red cell units transfused was lower in the restrictive strategy group (2 vs. 4). The FACT‐BMT total score was higher at all time points for patients in the restrictive transfusion group including at baseline (109 vs. 103) and at 100 days (116·3 vs. 109·2). After adjustment for baseline, the FACT‐BMT score at day 100 in the restrictive group was statistically non‐inferior to the liberal group (P < 0·0001). There were no significant differences between the two groups for any other clinical outcomes. Based on the results of the TRIST trial, a restrictive haemoglobin threshold of 70 g/l should become standard practice in haematopoietic stem cell transplant patients, and, given the lack of other clinical studies, all other haematology–oncology inpatients.     

HLA-E polymorphisms in hematopoietic stem cell transplantation

Human leukocyte antigen (HLA)-E is an inhibitory ligand of natural killer cells and γ/δ T-cells. Differential expression of HLA-E alleles on the cell surface has been reported to influence outcome of hematopoietic stem cell transplantation (HSCT). We performed HLA-E genotyping in 116 HSCT patients and their HLA-matched unrelated donors. The impact of HLA-E genotypes on patient's overall survival (OS), disease free survival (DFS), cumulative incidences for relapse, transplant-related mortality (TRM) and acute graft vs host disease (aGvHD) was assessed. Neither univariate nor multivariate analysis showed any influence of HLA-E polymorphisms on the investigated endpoints of HSCT in our cohort. We could not confirm any of the previous observations in our cohort and consider it unlikely that HLA-E polymorphisms affect outcome of HSCT.     

Oncolytic virotherapy in hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is a curative option for various hematologic malignancies. However, fatal complications, such as relapse and graft-versus-host disease (GVHD) hampered favorable HSCT outcomes. Cancer cells remained in the body following the conditioning regimen, or those contaminating the autologous graft can cause relapse. Although the relapse is much lesser in allogeneic HSCT, GVHD is still a life-threatening complication in this type of HSCT. Researchers are seeking various strategies to reduce relapse and GVHD in HSCT with minimum effects on the engraftment and immune-reconstitution. Oncolytic viruses (OVs) are emerging anti-cancer agents with promising results in battling solid tumors. OVs can selectively replicate in the malignant cells in which the antiviral immune responses have defected. Hence, they could be used as a purging agent to eradicate the tumoral contamination of autologous grafts with no damages to hematopoietic stem cells. Moreover, they have been shown to alleviate GVHD complications through modulating alloreactive T cell responses. Primary results promise using OVs as a strategy to reduce both relapse and GVHD in the HSCT without affecting hematologic and immunologic engraftment. Herein, we provide the latest findings in the field of OV therapy in HSCT and discuss their pros and cons.