白细胞介素1在免疫应答反馈调节中的作用

<正> 白细胞介素 1(IL-1)具有多种生物学活性,对许多细胞都有刺激作用。在免疫反应中,IL-1参与抗原或丝裂原对T细胞的激活,可促进白细胞介素2(IL-2)及 IL-2受体的产生;IL-1还可增强B细胞产生抗体的能力,它是促进免疫应答的一种重要因子。此外,IL-1在免疫应答的反馈调节中也起着重     

白细胞间介素—2受体

白细胞间介素-2(IL-2)是在巨噬细胞分泌的白细胞间介素-1(IL-1)存在下,由抗原/丝裂原活化某些 T 细胞合成和分泌的一种淋巴因子。在体外,IL-2能刺激活化 T细胞克隆的长期生长,增强胸腺细胞的有丝分裂反应,诱导胞毒性 T 细胞活性和增强裸鼠脾细胞培养中的空班形成细胞反应。在体内,IL-2可能用于治疗一些免疫性疾病如获     

IL-2基因缺陷小鼠T细胞的发育及其功能改变

白细胞介素2(IL-2)是由活化T 淋巴细胞亚群分泌的淋巴因子,在免疫应答中起着关键作用,它能促进T 细胞生长,但它并非仅作用于T 细胞,还有促进NK 细胞生长及B 细胞分化的作用;它对T 细胞发育的作     

类风湿患者和正常人的树突状细胞产生IL-1活性

白细胞介素1(IL-1)有多种生物学活性,包括促使激活的T细胞产生白细胞介素2(IL-2)和表达IL-2受体、致热原作用及促使肝细胞产生急性期反应物等。单核细胞是产生IL-1的主要细胞,但角质细胞、星形胶质细胞及神经胶质细胞等也可产生。已证明,在各种T细胞的免疫应答中,树突状细胞(DC)可能是较单核细胞(MO)或巨噬细胞更有效的辅佐细胞,但其是否能     

小儿肾病综合征时外周血T淋巴细胞功能的研究

为研究细胞免疫功能紊乱在小儿肾病综合征发病机理中的作用,我们对48例患儿外周血淋巴细胞产生的白细胞介素-2(Interleukin-2,IL-2)活性、T淋巴细胞亚群及白细胞介素-2受体(IL-2receptor,IL-2R)进行了测定。结果表明:①肾病期IL-2活性及IL-2R表达下降,T细胞亚群失衡,并与疾病的活动性有关。②肾病期IL-2活性水平与CD4~ 细胞百分率、CD4~ /CD8~ 细胞比值呈正相关,分泌IL-2的T细胞数量减少,可能是肾病患儿IL-2活性下降的原因之一。③肾病期IL-2活性变化与血清IgG含量变化呈正相关,IL-2活性下降可能是低IgG血症的原因之一。这些结果提示:T淋巴细胞功能受损,免疫应答能力下降,是小儿肾病综合征的重要表现。因此,适当选用免疫调节剂提高机体免疫水平,对疾病治疗会有一定益处。     

人IL-2、NK活性及免疫干扰素的研究——Ⅱ、鼻咽癌患者外周血单核细胞产生IL-2活性水平及其与IFNr产生和NK活性的关系

白细胞介素-2(IL-2)是一种由T细胞产生的淋巴因子。大量的研究资料表明,IL-2不仅能支持T细胞的生长与增殖,还广泛地参与对免疫应答的调节,如促进自然杀伤细胞(NK细胞)活性、调节免疫干扰素(IFNr)的产生和影响B细胞的增殖及抗体     

白细胞介素-2受体蛋白

成熟T淋巴细胞对抗原刺激的增殖应答受淋巴因子白细胞介素-2(IL-2)的调控。由于受抗原的激活,辅助T细胞亚群产生IL-2,并诱导T细胞呈现特异性IL-2受体。激活的T细胞可表达对IL-2亲和力不相同的二类IL-2受体。约10％的受体为高亲和力[解离常数(Kd)～10pM],以介导T细胞对IL-2的生理应答,其余的受     

有关IL-4研究的现况

<正> 已经鉴定并正式命名的白细胞介素(interleukin)有三种,即IL-1,IL-2,IL-3。IL-1是巨噬细胞分泌的,它的作用是促进胸腺细胞、T细胞和纤维母细胞的增殖分化,诱导T_H细胞产生IL-2。IL-2是由T_H细胞、NK细胞分泌的T细胞生长因子,它具有广泛促进免疫反应的作用。IL-3也是T_H细胞分泌的,它诱导巨噬细胞分泌IL-1;同时,它亦是造血系统的调节因子,又称为泛成血因子(panspecific hemopoietin);它可诱导20-α-羟基类固醇脱氢酶的分泌(其它因子亦可诱导此酶的分泌)。近来又提出IL-4。白细胞介素是当今前沿的研究课题,从事这方面     

IL—7的生物学作用

IL-7除刺激B细胞前体细胞成熟外,还可刺激成熟的T细胞增殖,增强T细胞的作用和淋巴因子的反应性;促进CTL、LAK、NK细胞的产生;诱导单核细胞分泌细胞因子IL-L0、IL-1p、IL-6、TNF-a、IFN-7等,且与ConA、PMA、IL-4、IL-12、IL-2等发生协同作用。分泌IL-7的肿瘤细胞致瘤率明显低下,可以作为肿瘤疫苗,同时它在抗肿瘤转移中具有一定的作用。     

亚硒酸钠对体外培养的慢性乙型肝炎患者外周树突状细胞功能的影响

目的： 体外培养慢性乙型肝炎患者外周树突状细胞（DCs）,检测其经过亚硒酸钠作用后功能的改变。方法：(1)建立用人重组粒细胞－单核细胞刺激集落因子（GM-CSF）、人重组IL-4、人重组IFN-α等细胞因子诱导、AIM-V培养外周血单个核细胞的方法。(2)收集慢性乙肝患者30例外周血，每份血分成2份，在诱生中不加亚硒酸钠处理者为乙肝组，加硒者为加硒组。健康献血者18例为对照组。(3)透射电镜观察其形态；MTT法检测DCs对同种异体淋巴细胞的增殖能力(MLR)及ELISA法检测细胞因子IL-12的分泌和GSH-Px、MDA的活性。结果：(1)DCs分泌IL-12水平和刺激淋巴细胞反应能力：乙肝组明显低于对照组(P<0.05)；加硒组比乙肝组高 (P<0.05)。(2)DCs细胞内的GSH-Px、MDA的活性：GSH-Px活性乙肝组明显低于对照组(P<0.05)；加硒组高于乙肝组和对照组(P<0.05)。MDA的活性乙肝组明显高于加硒组、对照组(P<0.05)。结论： 乙肝患者DCs功能缺陷可能与HBV感染DCs后产生的氧自由基损伤和GSH-Px过度消耗有关。体外经亚硒酸钠作用后的乙肝患者的DCs功能可在一定程度上恢复，可望为以后基于DCs的慢性乙型肝炎的免疫治疗提供新思路。     

Role of Zinc in Interleukin 2 (IL-2)-Mediated T-Cell Activation

In a serum-free culture containing no zinc, zinc enhanced the proliferation of T cells in response to interleukin 2 (IL-2), and also the in vitro production of IL-2 by T cells. Although the lymphocyte proliferation was partially inhibited by anti-IL-2 antibodies, it was completely inhibited by anti-IL-2 receptor (CD25) antibodies. A Scatchard plot analysis showed that zinc induced the expression of high-affinity receptors for IL-2 on lymphocytes. The results indicated that zinc may be essentially required for IL-2-mediated T-cell activation.     

Interleukin 10 Inhibits TNF-Alpha Production in Human Monocytes Independently of Interleukin 12 and Interleukin 1 Beta

Previously we demonstrated that endogenously produced Interleukin (IL-)IO suppressed the production of tumor necrosis factor-alpha (TNF-alpha) in CD3 activated T-cells via downregulation of paracfine IL-12 secretion from APC. Here we investigated the effect of endogenous IL-10 on TNF-alpha production in purified lipopolysaccharide (LPS) stimulated monocytes and its mechanism. Similarly to its effects on T-cells, EL-10 inhibited monocyte TNF-alpha production by about half Unlike in T-cells, however, this effect was not mediated via IL-12. While blockade of endogenous IL-10 binding to the IL-10 receptor enhanced the autocrine production of TNF-alpha, IL-12 and IL-1 beta, the neutralization of IL-12 or IL-1 beta did not affect the EL-10 effects on TNF-alpha production. This suggests that despite its inhibitory effects on IL-12 and IL-1 beta, which is quite similarly observed in T-cells, in purified monocytes IL-10 does not effect its TNF-alpha suppression by this mechanism. These findings indicate that IL-10 regulates production of pro-inflammatory cytokines by distinct mechanisms in different cells and tissues. Our study thus adds to the appreciation of the complex cytokine regulation of the immune system.     

Interleukin 10 Inhibits TNF-Alpha Production in Human Monocytes Independently of Interleukin 12 and Interleukin 1 Beta

Previously we demonstrated that endogenously produced Interleukin (IL-)IO suppressed the production of tumor necrosis factor-alpha (TNF-alpha) in CD3 activated T-cells via downregulation of paracfine IL-12 secretion from APC. Here we investigated the effect of endogenous IL-10 on TNF-alpha production in purified lipopolysaccharide (LPS) stimulated monocytes and its mechanism. Similarly to its effects on T-cells, EL-10 inhibited monocyte TNF-alpha production by about half Unlike in T-cells, however, this effect was not mediated via IL-12. While blockade of endogenous IL-10 binding to the IL-10 receptor enhanced the autocrine production of TNF-alpha, IL-12 and IL-1 beta, the neutralization of IL-12 or IL-1 beta did not affect the EL-10 effects on TNF-alpha production. This suggests that despite its inhibitory effects on IL-12 and IL-1 beta, which is quite similarly observed in T-cells, in purified monocytes IL-10 does not effect its TNF-alpha suppression by this mechanism. These findings indicate that IL-10 regulates production of pro-inflammatory cytokines by distinct mechanisms in different cells and tissues. Our study thus adds to the appreciation of the complex cytokine regulation of the immune system.     

Interleukin 4 inhibits the interleukin 2-induced production of its functional antagonist, interferon gamma

Interferon gamma (IFN gamma) inhibits many effects of interleukin (IL)-4. Its production largely parallels cell proliferation but is regulated independently. As IL-4 inhibits several IL-2-induced effects including proliferation of human peripheral blood mononuclear cells, we investigated its influence on the IL-2-induced IFN gamma production. We found that both absolute IFN gamma production and IFN gamma production per proliferation unit (1000 cpm) in response to IL-2 were inhibited by IL-4. IL-2-induced interferon production was inhibited by IL-4 in both sheep red blood cell rosetting and non-rosetting cells. In bidirectional mixed lymphocyte culture, IL-4 alone enhanced proliferation but suppressed IFN gamma production. As 48% of IFN gamma-producing cells are known to show T cell phenotype, the nearly total inhibition of IFN gamma production is evidence for suppression of T cell response to IL-2. Additionally, we found that the inhibition of IL-2-induced proliferation by IL-4 was significantly more pronounced at low cell densities. Basal proliferation was only inhibited in serum-containing media. These data stress the importance of other lymphokines or accessory cells in the regulation of early lymphocyte activation.     

Interleukin 1 plays a major role in the development of Th2-mediated immunity

Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th)2-type response, involving interleukin (IL)-4, IL-9 and IL-13. Here, we show that Th2 response-associated resistance is dependent on the presence of IL-1alpha and IL-1beta. When lymph node cells from naive IL-1alpha- or IL-1beta-deficient mice were subjected to Th2 polarization in vitro, they failed to polarize in the presence of IL-4 alone, but required the addition of exogenous IL-1alpha or IL-1beta. Furthermore, we demonstrate that both IL-1alpha- and IL-1beta-deficient mice are susceptible to chronic T. muris infection and that the inability to expel the worms is associated with a defect in the development of a Th2 response in the mesenteric lymph nodes. These results provide the first demonstration of the critical role of IL-1 in regulating Th2 responses during gastrointestinal nematode infection.     

Polymorphisms of Interleukin 4 Receptor Gene and Interleukin 10 Gene are not Associated with Graves' Disease in the UK

Graves' disease (GD) is an autoimmune disorder of the thyroid gland and both environmental and genetic factors contribute to disease aetiology. Cytokines, such as interleukin 4 (IL-4) and interleukin 10 (IL-10), are involved in the immune response and may be implicated in the autoimmune disease process. Associations have been reported between single nucleotide polymorphisms (SNPs) of IL-10 and the Ile50Val polymorphism of the IL-4 receptor gene (IL-4R) gene and atopy and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The autoimmune diseases cluster within families and susceptibility genes may overlap between the different disorders. Therefore, we investigated 5 SNPs (-592C/A, -657G/A, -819C/T, -1349A/G, and -2013G/A) in the promoter region of the IL-10 and the Ile50Val polymorphism (A/G) in the IL-4R in a large UK population based case-control dataset with GD. No association was found between the polymorphisms studied and GD and no significant differences were found in genotype or allele frequencies between the patients and control subjects. We conclude these polymorphisms of IL-10 and IL-4R previously associated with other immune mediated diseases, do not confer susceptibility to GD in white Caucasians in the United Kingdom.     

Trypanosoma cruzi trans-Sialidase Prevents Elicitation of Th1 Cell Response via Interleukin 10 and Downregulates Th1 Effector Cells

The trans-sialidases (TSs) from Trypanosoma cruzi, the agent of Chagas disease, are virulence factors shed to the bloodstream that induce strong alterations in the immune system. Here, we report that both enzymatically active TS (aTS) and its lectinlike isoform (iTS) disturb CD4 T cell physiology, inducing downregulation of Th1 cell functionality and in vivo cell expansion. By using ovalbumin-specific DO11.10 cells as tracers of clones developing the Th1 phenotype, we found that the infection induced significant amounts of gamma interferon (IFN-γ) but low levels of interleukin 2 (IL-2) and increased IL-4 production in vivo, in agreement with a mixed T helper response. The production of cytokines associated with the Th2 phenotype was prevented by passive transfer of anti-TS neutralizing antibodies. TSs also reduced the T cell receptor signaling as assayed by Zap-70 phosphorylation. TSs also reduced IL-2 and IFN-γ secretion, with a concomitant increase in IL-4 production and then an unbalancing of the CD4 T cell response toward the Th2 phenotype. This effect was prevented by using anti-IL-10 neutralizing antibodies or IL-10^−/− antigen-presenting cells, supporting the subversion of this regulatory pathway. In support, TSs stimulated IL-10 secretion by antigen-presenting cells during their interaction with CD4 T cells. When polarized cells were stimulated in the presence of TSs, the secretion of IL-2 and IFN-γ was strongly downregulated in Th1 cells, while IL-2 production was upregulated in Th2 cells. Although the Th1 response is associated with host survival, it may simultaneously induce extensive damage to infected tissues. Thus, by delaying the elicitation of the Th1 response and limiting its effector properties, TSs restrain the cell response, supporting T. cruzi colonization and persistence while favoring host survival.     

Interleukin 12 and innate molecules for enhanced mucosal immunity

Recent strategies for understanding the mechanisms underlying mucosal immune responses and subsequent development of mucosal vaccines for induction of targeted immunity now include cytokines and molecules of innate immunity. These studies have shown that cytokines influencing the development of T helper (Th) cells differentially affect the outcome of mucosal vs systemic immune responses to mucosal vaccines. Serum antigen-specific antibody (Ab) responses were enhanced when either IL-6 or IL-12 was mucosally administered with a protein antigen, while only IL-12 induced antigen-specific mucosal IgA Ab responses. Mucosal IL-6 and IL-12 also affected the type of Th cell responses induced by CD4⁺ T cells from mice that received IL-12 secreted larger amounts of IFN-γ and IL-6 when compared with mice nasally treated with IL-6. Discrepancies in the ability to enhance mucosal or systemic immune responses were also observed when human neutrophil peptide (HNP) defensins or lymphotactin were nasally coadministered with protein antigens. Only lymphotactin promoted mucosal secretory IgA (S-IgA) Ab responses while both lymphotactin and defensins enhanced systemic immunity to mucosally co-administered protein antigens. Mixed antigen-specific Th1-and Th2-type CD4⁺ T cell responses were induced in the systemic compartment by both lymphotactin and the mixture of HNP-1, HNP-2, and HNP-3 defensins. However, HNPs failed to significantly enhance cytokine secretion by mucosally derived, antigen-specific CD4⁺ T cells relative to those isolated from the systemic compartment. In summary, these studies clearly show that IL-12 and lymphotactin are able to trigger S-IgA Ab responses and provide new avenues for the design of safe and targeted mucosal vaccines.     

Intradermal Recombinant Interleukin 2 Enhances Peripheral Blood T-Cell Responses to Mitogen and Antigens in Patients with Lepromatous Leprosy

Thirty-one patients with lepromatous leprosy received recombinant interleukin 2 (IL-2) intradermally in doses ranging from 10 to 30 micrograms. Before injection and at time intervals of 2-21 days thereafter, samples of peripheral blood mononuclear cells (PBMC) were obtained. Single or multiple injections (1-3) of IL-2 did not modify the total number of circulating lymphocytes or the number of T cells and the CD4/CD8 T-cell ratio. However, IL-2 had a pronounced influence on the [3H]thymidine incorporation in response to various stimuli 4-8 days after intradermal IL-2. Stimulation indices of three- to sevenfold above pre-IL-2 levels were observed with the polyclonal activator phytohaemagglutinin (PHA) and enhanced thymidine incorporation occurred in the presence of antigens to which the patients were already sensitized, such as purified protein derivative and BCG. IL-2 had no effect on the unresponsive state of lepromatous leprosy patient T cells to the antigens of Mycobacterium leprae.     

Regulation of IgG1 and IgE Synthesis by Interleukin 4 in Mouse B Cells

Mouse interleukin 4 (IL-4) has been shown to act on B cells as an induction factor for Ig class switch. We studied the characteristics of IL-4-regulated Ig isotype production in lipopolysaccharide (LPS)-stimulated splenic B-cell cultures with emphasis on the comparison between the IgG1 and IgE responses. The results show that the kinetics for the appearance of IgG1 and IgE isotypes are similar, but that the dose of IL-4 required for the induction of an IgE response is 3-10 times higher than that for an IgG1 response. No requirement for T cells was found for the induction of either isotype. Pre-incubation of cells for 24 h with IL-4 alone was sufficient to induce an IgG1 response when cells were recultured with LPS from days 1 to 6. However, the simultaneous presence of both IL-4 and LPS for at least 24 h was required for a detectable IgE response. For an optimal IgE response, IL-4 needed to be present for more than 72 h in LPS-activated cultures. The possible reasons for the different regulation of IgG1 and IgE responses are discussed.