自然杀伤细胞与肿瘤免疫治疗的研究进展

自然杀伤(NK)细胞是一种独特的淋巴细胞，形态上像大颗粒淋巴细胞，但缺乏膜表面免疫球蛋白或T细胞受体。NK细胞有表面受体，能接受周围环境的各种信号，决定对外来病原体和肿瘤细胞的反应。NK细胞能够杀死不同来源的肿瘤细胞，在肿瘤免疫监视和肿瘤免疫治疗中发挥重要作用。NK细胞通过产生效应分子直接抑制肿瘤生长和向其他免疫系统传递重要信息。NK细胞在肿瘤免疫治疗中作用的体外研究很多，但临床应用仍处于实验阶段。     

树突状细胞与肿瘤免疫治疗

树突状细胞的生物学特征及其在免疫应答中的重要作用,使之成为当前肿瘤免疫治疗研究的热点。树突状细胞是目前已知功能最强的抗原呈递细胞,可在体内活化CD4+、CD8+T细胞,从而激发一系列的特异性免疫应答。本文就其特性及在抗肿瘤免疫中的作用作一综述。     

白细胞介素-15与肿瘤的免疫治疗

近年来，许多研究表明白细胞介素-15(IL-15)与肿瘤的发生、发展关系密切。一方面，它能扩增和激活自然杀伤细胞、CD8^ T细胞，增强机体的免疫力。另一方面，IL-15的不正确表达则对机体造成损害。故通过增加外源性IL-15来提高机体的免疫力和清除不正确表达的IL-15是肿瘤免疫治疗中两个主要方向。     

白细胞介素-15与肿瘤的免疫治疗

近年来 ,许多研究表明白细胞介素 1 5 (IL 1 5 )与肿瘤的发生、发展关系密切。一方面 ,它能扩增和激活自然杀伤细胞、CD8+ T细胞 ,增强机体的免疫力。另一方面 ,IL 1 5的不正确表达则对机体造成损害。故通过增加外源性IL 1 5来提高机体的免疫力和清除不正确表达的IL 1 5是肿瘤免疫治疗中两个主要方向     

树突状细胞与肿瘤免疫治疗

树突状细胞的生物学特征及其在免疫应答中的重要作用，使之成为当前肿瘤免疫治疗研究的热点。树突状细胞是目前已知功能最强的抗原呈递细胞，可在体内活化CD4^ ,CD8^ T细胞，从而激发一系列的特异性免疫应答。本文就其特性及在抗肿瘤免疫中的作用作一综述。     

树突状细胞与肿瘤免疫治疗

树突状细胞(dendritic cell,DC)是一类功能最强的抗原提呈细胞(antigen present cell,APC),它能有效地刺激初始型T淋巴细胞的增殖反应,是机体免疫反应的始动者。DC激活的细胞毒性T淋巴细胞(cytotoxic T lymphocytes,CTLs)所介导的细胞毒作用在机体抗肿瘤免疫中起着重要作用。 一、DC的特征 成熟DC的特征为细胞表面表达丰富的MHC-Ⅰ、Ⅱ类分子,共刺激分子B7-1(CD80)和B7-2     

儿童食物过敏免疫治疗研究进展

儿童食物过敏的发生率逐年增加,目前对食物过敏的治疗主要是缓解症状而难以治愈.随着分子免疫学的发展及对食物过敏发生机制等的深入研究,一些行之有效的治疗措施正应用于临床.该文就食物过敏的免疫治疗方法,包括T细胞肽及重组致敏蛋白突变免疫疗法、免疫刺激的DNA序列、辅助T细胞激活作用的抑制、过敏诱导的细胞因子的抑制及炎性细胞迁移的抑制等作一综述.     

病毒性心肌炎免疫发病机制及免疫治疗的研究进展

病毒感染诱发的免疫反应与病毒性心肌炎的组织损伤有着密切的联系，近年来对免疫发病机制的研究主要有以下几个方面：T细胞介导的细胞免疫反应、B细胞介导的体液免疫反应以及细胞因子的共同作用。免疫治疗的新进展主要有：免疫抑制剂对机体免疫系统的抑制、免疫球蛋白的免疫调节治疗、周围免疫耐受的诱导及疫苗的应用。     

NK细胞活性在小儿哮喘尘螨特异性免疫治疗中的意义

目的探讨自然杀伤（NK）细胞活性在小儿哮喘尘螨特异性免疫治疗中的意义。方法分别检测尘螨过敏的哮喘患儿58例、正常对照组儿童30例NK细胞活性,并对哮喘患儿进行尘螨特异性免疫治疗,治疗前后检测其NK细胞活性及总IgE。结果哮喘患儿的NK细胞活性比正常对照组显著减少（P〈0．01）;尘螨特异性免疫前较特异性免疫后的哮喘患儿的NK细胞活性显著增高（P〈0．01）,总IgE显著降低（P〈0．01）。结论NK细胞参与哮喘的发病过程,是一种重要的免疫调节细胞。特异性免疫疗法有助于NK细胞活性增强,降低总IgE水平,从而减少哮喘的发作。     

特异性免疫治疗对哮喘患儿自然杀伤细胞和嗜碱性细胞的影响

目的探讨特异性免疫治疗哮喘患儿NK细胞活性和嗜碱性细胞表达变化的意义。方法将60例轻、中度哮喘患儿(均对屋尘螨过敏)分为两组,其中治疗组30例,采用屋尘螨特异性免疫治疗联合吸入糖皮质激素为主的哮喘防治方案;对照组30例,仅采用吸入激素为主的哮喘防治方案。检测两组治疗前后NK细胞活性和嗜碱性粒细胞表达以及血清总IgE、屋尘螨特异性IgE(DP-IgE)、嗜酸性细胞阳离子蛋白(ECP)水平,评价两组患儿治疗前后哮喘急性发作次数,比较治疗前后哮喘控制测试(C-ACT)评分和最大用力呼气峰流速(PEF)测试结果。结果治疗组治疗后外周血NK细胞活性(12.01±1.41)%,明显高于对照组(10.11±2.49)%(t=3.83,P=0.00)。治疗组治疗后嗜碱性粒细胞含量、血清总IgE及DP-IgE水平下降程度均明显高于对照组(Z=2.23~3.57,P均<0.05);治疗后两组哮喘急性发作次数较治疗前均明显减少,C-ACT评分和PEF结果较治疗前均有提高,治疗组更优于对照组,差异有统计学意义(t=3.63~4.02,P均<0.01)。结论特异性免疫治疗联合规范化防治使哮喘患儿病情更趋稳定,哮喘控制效果更理想。特异性免疫治疗能显著提高机体NK细胞活性、减少嗜碱性粒细胞含量。     

Cytotoxic function of umbilical cord blood natural killer cells: relevance to adoptive immunotherapy

Decreased graft-versus-host disease (GVHD), ease of accessibility, and sustained engraftment encourage the use of umbilical cord blood (UCB) as an alternative source to bone marrow for immune reconstitution in children with leukemia. Natural killer (NK) cells rapidly expand after stem cell transplantation and are important for regulating GVHD and providing graft-versus-leukemia (GVL) effects. This review highlights the phenotypic and functional differences between UCB NK cells and adult peripheral blood (APB) NK cells, and discusses the possible therapeutic benefit of using UCB NK cells for adoptive immunotherapy in leukemia. Alloreactive NK cells show potent cytotoxic activities against human leukocyte antigen (HLA)-nonidentical leukemic cells and reduce leukemia relapses. The higher numbers of NK progenitors in UCB makes it a convenient source for ex vivo expansion of UCB NK cells for posttransplant treatment. UCB NK cells readily respond to interleukin-15, which may greatly enhance their antitumor effect. Activation and expansion protocols for UCB NK cells are currently being developed.     

Adoptive cellular immunotherapy with CD19-specific T cells

BACKGROUND: No effective therapeutic modalities exist for the treatment of relapsed high risk acute lymphoblastic leukemia (ALL). Adoptive cellular immunotherapy by transfusion of polyclonal donor lymphocytes is not always effective and is limited by cellular cross-reactivity with normal tissues, leading to development of clinical graft-versus-host disease (GVHD). METHOD: To develop an immunotherapeutic strategy for targeted elimination of residual leukemic blasts, human T cells were gene-modified to express CD19-specific chimeric receptors. RESULTS: Gene-modified T cells specifically lyse CD19-expressing lymphatic blast cells, however, they show a limited proliferative response to stimulation with CD19. Integration of the signal transduction domain of the costimulatory molecule CD28 enhances the proliferative properties of the gene-modified T cells. CONCLUSIONS: Adoptive transfer of gene-modified virus-specific T cells may provide a useful strategy for prevention and early treatment of ALL relapses following allogeneic stem cell transplantation.     

Chronic natural killer cell lymphocytosis is associated with elevated cytotoxic activity of natural killer cells

The authors describe a 16-year-old girl who has suffered from chronic natural killer cell lymphocytosis (CNKL) for 12 years. From age 4 years, she has shown a persistent lymphadenopathy and lymphocytosis. Clinically, she developed allergic skin involvement, thrombocytopenia, and peripheral polyneuropathy. Annual flow cytometry analyses of lymphocyte subsets revealed persistently elevated NK cell levels (55-75% of the lymphocyte fraction and 0.7-10 x 10(3) NK cells per microliter of blood). Furthermore, IgE serum concentrations were markedly increased. Based on CD16, CD161, and CD94 surface antigen expression, the NK cell population was characterized as mature NK cells. Functional analysis of these cells showed a 2-fold increase of intrinsic cytotoxic activity toward K-562 cells compared with NK cells from healthy controls. The authors present a clinical case of rare CNKL. The patient's NK cells possess significantly increased cytotoxic activity. These findings are discussed in context with elevated IgE concentrations.     

Cytotoxic T cells and immunotherapy

Promising immunotherapies for viral infections and malignancies reflect the successful, rapid translation of laboratory findings into clinical practice. Fletcher et al. [1] present imaging studies of Epstein-Barr virus (EBV)-associated lymphomas before and after immunotherapy. Here, we briefly review the scientific bases of such novel therapies, which have evolved from advances in understanding of immune effector cells, of the cytokines that drive immune responses, and of the mechanisms underlying cell death. Received: 9 February 1998 Accepted: 16 March 1998     

不同方式刺激脐血树突状细胞对细胞因子诱导杀伤细胞和自然杀伤细胞杀伤活性的影响

目前对造血干细胞移植(hematopoietic stem cell transplantation,HSCT)后残留肿瘤细胞的清除需通过过继免疫治疗等手段来解决.通过特定细胞因子联合扩增脐血中细胞因子诱导杀伤(cytokine-induced killer,CIK) 细胞、自然杀伤(natural killer,NK)细胞,可增强脐血移植(UCBT)后的移植物抗白血病(graft-versus-leukemia,GVL)效应.树突状细胞(dendritic cells ,DC)在免疫应答的诱导中具有独特地位,     

Human natural killer cells in health and disease

Natural killer (NK) cells are an essential component of the innate immune system and play a critical role in tumor immune surveillance. NK cells express their own repertoire of receptors (NKRs) that bind to major histocompatibility class I or class I-like molecules. The balance of signals from stimulation or inhibition of NKRs determines the ability of NK cells to lyse specific targets. In haploidentical stem cell transplantation with purified stem cells, NK cell alloreactivity (killer immunoglobulin-like receptor [KIR] mismatch) has been demonstrated to reduce the risk of relapse in acute myeloid leukemia. There is a need for adequately powered prospective randomized studies to determine the usefulness of NK cells as adoptive immunotherapy, optimal NK cell doses and timing of administration. Further studies are required to determine optimal selection of donors and recipients, both on NKR matching/mismatching, undergoing haploidentical and unrelated hematopoetic stem cell transplantation.