系统性红斑狼疮患者血清可溶性细胞间黏附分子-1、L-选择素及细胞因子浓度测定的临床意义

系统性红斑狼疮（systemic lupus erthmatosus。SLE）是一种以B淋巴细胞度活化，以抗dsDNA、抗sm等自身抗体为特征的、机体免疫调节系统紊乱所致的多系统受累的自身免疫性疾病。其中黏附分子则参与了T、B细胞活化以及T、B细胞之间的相互作用。细胞因子是各细胞产生的可溶性物质，体内各种反应均需要其参与。近来黏附分子和细胞因子在SLE中作用的研究日益受到重视。     

结核病患者外周血淋巴细胞及其亚群定量检测及临床意义

结核病的发病和转归与机体的免疫状态有关 ,尤其是细胞免疫功能。免疫功能正常的机体感染结核分支杆菌后 ,可以诱导T细胞活化 ,活化的T淋巴细胞产生各种细胞因子 ,从而杀灭结核分支杆菌 ,使机体免于发病或使病灶局限。若免疫功能异常则可导致发病或病灶恶化。自然杀伤细胞 (NK细胞 )及T淋巴细胞亚群的检测是研究细胞免疫功能的重要方法[1] 我们用流式细胞仪对 6 0例结核病患者外周血中的NK细胞、T淋巴细胞亚群及B细胞进行定量检测 ,旨在探讨NK细胞、T细胞亚群及B细胞改变在结核发病中的作用及临床意义。1　标本收集和检测方法1 1　病…     

白细胞介素-13在支气管哮喘中的作用

随着免疫学和分子生物学的发展，哮喘炎症研究的重点已经移到了T淋巴细胞上。T淋巴细胞通过释放多种细胞因子，在整个炎症反应中起着至关重要的作用，近年来，对T辅助细胞功能的认识取得重大进展，机体的Th1／Th2平衡倍受研究人员关注。哮喘的发生与Th2优势应答密切相关，Th2型细胞因子如白细胞介素（IL）-4、IL-5及IL-13分泌增加，     

裙带菜多糖对人外周血淋巴细胞因子分泌的影响

目的分析裙带菜多糖对人外周血淋巴细胞亚群、细胞因子分泌的影响,探讨裙带菜多糖的免疫调节机制。方法用流式细胞术检测淋巴细胞亚群的变化,用酶联免疫方法测定裙带菜多糖作用后淋巴细胞培养上清中细胞因子的浓度。结果不同浓度的裙带菜多糖可使CD+8T细胞比例明显增加(P<0.01);并可使CD+4T细胞比率增加,但与阴性对照组比较差异无统计学意义(P>0.05);裙带菜多糖对B细胞增殖反应无明显影响(P>0.05)。不同浓度的裙带菜多糖作用后,NK细胞比例明显增高(P<0.01),并呈浓度依赖性,可明显刺激外周血淋巴细胞产生白细胞介素-2(IL-2)(P<0.01),但对IL-6及IL-10的产生作用无明显影响(P>0.05)。结论裙带菜多糖可促进CD+8、NK细胞增殖,产生Th1类细胞因子发挥免疫调节作用。     

支气管哮喘急性期与缓解期血清白细胞介素-13测定的比较分析

支气管哮喘发病机制与变态反应、气道慢性炎症、气道高反应性及自主神经功能障碍等因素相互作用,共同参与哮喘的发病过程。血清白细胞介素-13(IL-13)与变态反应、气道慢性炎症、气道高反应性有关,白细胞介素-13是由活化的T细胞分泌的细胞因子,能诱导B细胞合成IgE,与机体的变态反应有关[1]。有研究证明辅助性T淋巴细胞(Th)能引起炎症和慢性组织损伤,IL-13作为Th2细胞因子,与机体的炎症反应和免疫调节等过程有关,可能参与多种肺部疾病发生、发展过程。本研究主要是探讨支气管哮喘患者血清I L-13的水平与病情变化关系,并与健康者进行比较…     

正常人外周血T细胞和T细胞亚群

胸腺依赖性淋巴细胞(T淋巴细胞)是参与机体细胞免疫的细胞群。近年证明,这是一个异质性的细胞群体。其中辅助性T细胞(Th)和抑制性T细胞(Ts)在许多疾病中的作用正日益受到重视。这两种细胞在机体内起着相互联系相互制约的作用,并和其它     

细胞因子用作治疗药物

细胞因子的产生是机体对病理状态的反应以恢复内环境稳定。治疗干预有时候通过给予细胞因子本身以支持机体的反应，起增效作用。有时候，疾病的表现是由细胞因子产生过多引起，就需要采用细胞因子拮抗剂治疗。细胞因子在癌症治疗，特别是对化疗及放疗后血细胞群的恢复可起很好作用。     

环胞菌素治疗的药学情况

作用方式骨髓和器官移植后发生急性排斥反应主要是归因于 T 淋巴细胞的作用。通过对外来组织的识别,使 T 细胞分化为三型(杀伤型、辅助型和抑制型)。在缺乏免疫抑制剂的情况下,过量杀伤型 T 细胞和辅助型 T 细胞导致机体对导体组织的排斥。环胞菌素能选择性地抑制杀伤型 T 细胞和辅助型 T 细胞的增殖,有利于抑制型 T 细胞的产生,而后者相应数     

T淋巴细胞凋亡信号途径与系统性红斑狼疮

正T淋巴细胞来源于骨髓中的淋巴样前祖细胞,在胸腺中发育成熟,具有介导细胞免疫应答并辅助机体产生体液免疫应答的功能。细胞凋亡(apoptosis)是程序性细胞死亡,机体通过凋亡机制清除衰老及异常细胞,在维持细胞数量平衡及正常功能方面有重要作用。T淋巴细胞功能异常和凋亡紊乱     

痤疮丙酸杆菌促树突状细胞前体细胞动员及其对胃癌的治疗效应

目的利用痤疮丙酸杆菌（P．aches）引起的炎症反应,促进小鼠外周血中树突状细胞（DC）的动员并研究P．aches动员的DC在体外对胃癌细胞的作用。方法C578BL／6J（B6）小鼠注射P．aches后外周血分离单个核细胞,用流式细胞仪分选F4／8013220-CD11c^＋细胞,在体外加入细胞因子GM-CSF、IL4和TNFα共培养,通过形态学观察、表型分析和混合淋巴细胞反应鉴定它们是否能分化为成熟DC。将P．aches动员的DC负载胃癌抗原后致敏T细胞,观察活化的T细胞在体外对胃癌细胞的杀伤效应。结果注射P．aches1h后外周血F4／80B220-CD11c^＋细胞数量即开始升高,24h后逐渐达到高峰。新鲜分离的细胞不具有成熟DC的特征。与细胞因子共培养后即具有典型的DC形态和表型,在混合淋巴细胞反应中具有极强的刺激T细胞增殖的能力。P．aches动员的DC负载胃癌抗原后致敏T细胞对胃癌细胞的杀伤率明显高于未致敏T细胞。结论P．aches可迅速动员F4／80-B220-CD11c^＋细胞进入小鼠外周血,经细胞因子的诱导后可分化为成熟DC,并可在体外诱导出针对胃癌细胞的特异性杀伤T淋巴细胞,对胃癌细胞有明显的杀伤作用,并伴有高水平的INF-γ分泌。     

Recent patents on topical application of honey in wound and burn management

Topical application of honey to burn and wounds has been found to be effective in controlling infection and producing a clean granulating bed. It is suggested that the wound healing effect of honey may in part be related to the release of inflammatory cytokines from surrounding tissue cells, mainly monocytes and macrophages. It has been reported that honey hastens wound healing by accelerating wound contractions. Microscopic evaluation demonstrated that there was a significant acceleration of dermal repair in wound treated with honey. Macroscopic and microscopic observations under in vivo assessment suggested that the topical application of honey might have favourable influences on the various phases of burn and wound healing hence accelerating the healing process. The regulatory effects of honey are related to components other than the sugars. However, the mechanisms by which honey affects the release of anti inflammatory agents and growth factors from monocytic cells are as yet unclear. Whether honey affects other cell types, particularly endothelial cells and fibroblasts, involved in wound healing also needs to be clarified. The present article is a short review of recent patents on the healing effect of honey in wound and burn management.     

The innate immune system,toll-like receptors and dermal wound healing: A review

Wound healing is a complex physiological process comprised of discrete but inter-related and overlapping stages, requiring exact timing and regulation to successfully progress, yet occurs spontaneously in response to injury. It is characterised by four phases, coagulation, inflammation, proliferation and remodelling. Each phase is predominated by particular cell types, cytokines and chemokines. The innate immune system represents the first line of defence against invading microorganisms. It is entirely encoded with the genome, and comprised of a cellular response with specificity provided by pattern recognition receptors (PRRs) such as toll-like receptors (TLRs). TLRs are activated by exogenous microbial pathogen associated molecular patterns (PAMPs), initiating an immune response through the production of pro-inflammatory cytokines and further specialist immune cell recruitment. TLRs are also activated by endogenous molecular patterns termed damage associated molecular patterns (DAMPs). These ligands, usually shielded from the immune system, act as alarm signals alerting the immune system to damage and facilitate the normal wound healing process. TLRs are expressed by cells essential to wound healing such as keratinocytes and fibroblasts, however the specific role of TLRs in this process remains controversial. This article reviews the current knowledge on the potential role of TLRs in dermal wound healing where inflammation arising from pathogenic activation of these receptors appears to play a role in chronic ulceration associated with diabetes, scar hypertrophy and skin fibrosis.     

The effect of AgK114 on wound healing

AgK114 is a newly isolated membrane-associated protein which is expressed on keratinocytes. Its expression is restricted to dermal sheath cells near sebaceous glands in normal skin. However, it is transiently induced by UV exposure or injury stimulation (Tatefuji T. et al., Biol. Pharm. Bull., 27, 1742-1749, 2004). Thus, the expression pattern of AgK114 suggested its potential role in wound healing response. We report here that expression of AgK114 is induced in the initial 24 h at the edge keratinocytes during keratinocyte migration, followed by disappearance once epithelialization is completed in the murine excisional wound model. We also demonstrate that exogenous recombinant mouse AgK114FL promoted wound healing process. Mouse AgK114FL up-regulated pro-matrix-metalloproteinase-9, vascular endothelial growth factor, transforming growth factor-beta, IL-6, and IL-1beta production in the early stage of wound tissue. Moreover, mouse AgK114FL induced the matrix-metalloproteinase-9 activity of wound fibroblasts prepared from impaired skin in the presence of proinflammatory cytokines. These results suggest that the AgK114 participates in the wound response during the healing process, and promotes wound repair.     

Targeting cytokines of the interleukin-12 family in autoimmunity

In the past, autoimmunity was thought to be mediated by antibodies and immune complexes. It has now become clear that many autoimmune diseases, especially tissue specific, are T cell-mediated, or at least T cell-dependent. The pathogenesis of cell-mediated autoimmune diseases, including multiple sclerosis, uveitis, diabetes, arthritis, and others, is now thought to be, in a large measure, driven by interferon-gamma-producing, antigen-specific T cells, which are polarized toward the T helper type 1 (Th1) phenotype. Interleukin (IL)-12 and the more recently discovered IL-23 and IL-27 constitute a unique family of structurally-related, heterodimeric cytokines, which regulate cell-mediated immune responses and Th1-type inflammatory reactions. Thus, these cytokines may have a central role in the development and progression of cell-mediated autoimmune diseases. Therefore, pharmacologically targeting cytokines of the IL-12 family would be useful in the modulation of several autoimmune diseases. This review summarizes the recent findings concerning IL-12 family cytokine-mediated autoreactive inflammatory responses, and also describes some possible therapeutic interventions, including medicinal compounds at mitigating autoimmune inflammation.     

Effect of Thuja occidentalis and its polysaccharide on cell-mediated immune responses and cytokine levels of metastatic tumor-bearing animals

Context: Tumor microenvironment induces an active immune tolerance and escapes immune surveillance. In order to achieve an effective antitumor immune response, appropriately activated immune cells should maintain their antitumor activity to overcome the immune suppressive tumor microenvironment.

Objectives: This study focuses on the effect of Thuja occidentalis L. (Cupressaceae) extract and its polysaccharide (TPS) on cell-mediated immune response (CMI) in metastasis bearing mice.

Materials and methods: Metastasis was induced by injecting B16F-10 melanoma cells in mice through the tail vein and effector mechanisms of CMI was studied by analyzing cytotoxic T-lymphocyte (CTL) activity, natural killer (NK) cell activity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ACC). The effect of T. occidentalis and TPS on pro-inflammatory cytokines and tissue inhibitor matrix metalloproteinases (TIMP) levels were also analyzed.

Results and discussion: Administration of T. occidentalis and TPS enhanced the NK cell activity, ADCC and ACC much earlier than the control tumor-bearing animals. T. occidentalis and TPS were also found to decrease the elevated level of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, GM-CSF and tumor necrosis factor (TNF)-α in the serum of metastatic tumor-bearing animals. The level of antitumor factors such as IL-2 and TIMP was elevated by the treatment with T. occidentalis and TPS in the serum, which was lowered in the untreated tumor-bearing animals.

Conclusion: This study clearly suggests that T. occidentalis and TPS effectively stimulate cell-mediated immune system and decrease pro-inflammatory cytokines, thereby inhibiting metastasis of tumor cells.     

Immunological safety evaluation of a haemostatic agent and wound dressing made of horse collagen fibrils

A haemostatic agent and wound dressing made of horse collagen (Tachotop) was applied to guinea-pigs in such a way that the intended use of this material in humans was simulated, and cell-mediated and humoral immune responses of the animals were investigated. In addition, immune reactions were forcefully induced in guinea-pigs in order to validate the methodical approach and quantitate the observed reactions. Cell-mediated immunity was measured as delayed-type hypersensitivity skin reactions, and antibodies were detected by an enzyme-linked immunosorbent assay (ELISA). Simulation of the intended application of this haemostyptic material did not induce immune reactions in guinea-pigs even under critical conditions. The animals could only be immunized when the antigen was administered in solution or finely dispersed and together with adjuvant. Immune reactions thus induced were specific for collagen, no reaction was obtained against possible impurities such as albumin, immunoglobulin or fibronectin. It is concluded--in accordance with clinical experience--that this material is very unlikely to induce immune reactions upon clinical application to humans.     

Target-independent Immune-cell Activation by Aggregates of T Cell-redirecting Bispecific Antibodies

T cell-redirecting bispecific antibodies (bsAbs) have been under development as a new class of biotherapeutics for cancer immunotherapy. T cell-redirecting bsAbs simultaneously bind tumor-associated antigens on tumor cells and CD3 on T cells, resulting in T cell-mediated cytotoxicity against tumor cells. In this study, we prepared a tandem scFv-typed bsAb targeting HER2 and CD3 (HER2-CD3), and evaluated the impact of aggregation of HER2-CD3 on the in vitro immunotoxicity. A cell-based assay using CD3-expressing reporter cells revealed that the aggregates of HER2-CD3 directly activated CD3-expressing immune cells in the absence of target antigen (HER2)-expressing cells. Comparison of the aggregates generated under various stress conditions indicated the possibility that insoluble protein particles, which were detected by qLD analysis and contained non-denatured functional domains, contributed to the activation of CD3-expressing immune cells. In addition, HER2-CD3 aggregates stimulated hPBMCs and strongly induced the secretion of inflammatory cytokines and chemokines. The cytokine/chemokine-release profiles suggested that the aggregates could induce inflammatory responses not only by CD3-mediated T cell activation but also by other immune cell activations. These results indicated the potential risk of aggregation of T cell-redirecting bsAbs, which could induce unwanted immune cell activation and inflammation and thereby immune-mediated adverse reactions.     

Targeting IL-17 in autoimmunity and inflammation

The discovery of two distinct subsets of helper T cells, IFN-γ-producing Th1 cells and IL-4-producing Th2 cells, about three decades ago enabled us to understand the immunopathology of cell-mediated and allergic inflammatory diseases in humans. The observation that T cell-mediated experimental autoimmune diseases can be induced in mice lacking Th1 and Th2 cell responses prompted many immunologists to hypothesize that there might be additional subsets in helper T cell population which mediate autoimmunity in the absence of Th1 and Th2 cells. Consequently, multiple independent research groups identified IL-17-expressing RORγt⁺CD4⁺ T cell population as a distinct subset of helper T cells which promotes autoimmune tissue inflammation. Subsequent studies have revealed that innate immune cells, including γδ T cells, NKT cells and innate lymphoid cells, also produce type 17 cytokines and contribute to tissue inflammation. In this review, we discuss our current understanding on the biology of IL-17 and the therapeutic potential of targeting IL-17 for the treatment of immune disorders in humans.     

T cell targeted immune enhancement yields effective T cell adjuvants

Given the critical role of cell-mediated immunity (CMI) in defense against attack from pathogens that establish chronic infections, it has become abundantly clear that current vaccine methodology will not be sufficient to develop the appropriate immune response for protection and/or clearance of infection. By extension, this logic also applies to cancer vaccines where T cell immune-mediated destruction is a critical mechanism for control of the disease. This review describes our current thoughts on the events associated with immune activation and evaluates the various approaches to achieve successful immune activation with defined or targeted antigens as opposed to using inactivated or attenuated organisms. The advantages and disadvantages of the current adjuvants for antigens that focus on mimicking the infection events via the innate immune system or antigen uptake are described in the context of generation of T cell specific responses. A central theme of the discussions is the importance of cytokines in modulating the immune response towards T cell immunity, either by adjuvant modulation or use of natural cytokine mixtures targeted towards the site of immune activation. Also discussed is the possibility that thymomimetic agents such as thymosin alpha1, levamisole and methyl inosine monophosphate (MIMP) may be useful in enhancing the T cell mediated arm of the immune response.