γc家族新成员:白细胞介素21

白细胞介素 2 1(Interleukin 2 1,IL 2 1)是最近发现的γc家族新成员 ,和IL 2、IL 15、IL 4高度同源 ,主要由活化的CD4 + T细胞产生。IL 2 1受体复合体由特异的IL 2 1受体识别亚单位和γc信号传导亚单位组成 ,高表达于胸腺、骨髓基质细胞、外周B细胞和NK细胞。IL 2 1能促进骨髓NK细胞增殖与分化 ,与抗CD4 0抗体协同刺激B细胞增殖 ,与抗CD3抗体协同刺激T细胞增殖。     

060 γc家族新成员:白细胞介素21

白细胞介素21(Interleukin 21,IL-21)是最近发现的γc家族新成员,和IL-2、IL-15、II-4高度同源,主要由活化的CD4+T细胞产生.IL-21受体复合体由特异的IL-21受体识别亚单位和γc信号传导亚单位组成,高表达于胸腺、骨髓基质细胞、外周B细胞和NK细胞.IL-21能促进骨髓NK细胞增殖与分化,与抗CD40抗体协同刺激B细胞增殖,与抗CD3抗体协同刺激T细胞增殖.     

白细胞介素15研究进展

ＩＬ－１５是新近发现的一种细胞因子，它广泛分布于外周单核细胞、上皮细胞和成纤维细胞中；能刺激Ｔ，Ｂ淋巴细胞增殖与分化，具类似于ＩＬ－２的生物学活性；能以高亲和力结合到多种淋巴细胞以及人内皮细胞、鼠胸腺细胞等血源和非血源细胞上；ＩＬ－１５Ｒ表现为ＩＬ－２Ｒβ和γ亚单位组成的高亲和力受体。     

γc家族新成员：白细胞介素2l

白细胞介素21(Interleukin 2l，IL-21)是最近发现的γc家族新成员，和IL-2、IL-15、IL-4高度同源，主要由活化的CD4^ T细胞产生。IL-21受体复合体由特异的IL-21受体识别亚单位和γc信号传导亚单位组成，高表达于胸腺、骨髓基质细胞、外周B细胞和NK细胞。IL-21能促进骨髓NK细胞增殖与分化，与抗CD40抗体协同刺激B细胞增殖，与抗CD3抗体协同刺激T细胞增殖。     

白细胞介素-21对免疫细胞的调节作用

IL-21在发挥生物学活性过程中与IL-2、IL-4、IL-9和IL-15等细胞因子受体共用γ链,均属于γc(共同γ链)依赖性细胞因子家族成员.     

白细胞介素21研究进展

IL 2 1是一种新近发现的细胞因子 ,主要由CD4 + T细胞分泌的 ,与其受体结合后可以调节B细胞的增生 ,促进T细胞、NK细胞的增殖、分化并能提高NK细胞杀伤活性 ,IL 2 1与多种疾病的发生有关。本文就IL 2 1及其受体的产生、分子结构、生物学作用及与疾病关系的研究进展作一综述。     

白细胞介素15

白细胞介素１５是在检测猴肾表皮细胞系ＣＶ－１／ＥＢＮＡ上清液中的细胞因子的活性过程中发现的一种新的细胞因子，分子量为１４～１５ｋＤ。ＩＬ－１５和ＩＬ－２有许多相似的生物学特性，可刺激ＣＴＬＬ和ＰＨＡ活化的外周血Ｔ细胞增殖；在体外可诱导ＣＴＬ和ＬＡＫ细胞的产生；通过ＪＡＫ－ＳＴＡＴ信号传导途径调节Ｔ细胞内基因表达；刺激Ｂ细胞增殖和分化；活化ＮＫ细胞。ＩＬ－１５的刺激作用需要与ＩＬ－２Ｒ的β链和γ链相作用，而不需α链。与ＩＬ－２不同之处是ＩＬ－１５可由人体多种组织和细胞产生，它对ＮＫ细胞的活化可能更为重要。如对ＩＬ－１５进行深入的研究，将使我们进一步认识它在正常宿主免疫中的作用。     

白细胞介素15的研究新进展

白细胞介素１５（ＩＬ－１５）是白细胞介素类新发现的一种细胞因子，能促进Ｂ细胞的分化增殖，诱导ＮＫ细胞增殖、细胞毒活性、细胞因子产生，它与ＩＬ－１２协同可促使ＮＫ细胞产生ＩＮＦ－γ，对于调节ＮＫ细胞的功能和机体免疫力有重要作用。ＩＬ－１５广泛分布于人体的组织和细胞，包括胎盘、骨骼肌、肾及活化的单核细胞／巨噬细胞，与白介素２（ＩＬ－２）共同享有某些生物学活性和受体组成。与ＩＬ－２同属４－螺旋束细胞因子     

白细胞介素16研究进展

白细胞介素-16（IL-16）过去称之为淋巴细胞趋化因子（Lymphocyte Chemotactic Factor,LCF)。主要由CD8^ T淋巴细胞分泌，属分泌型糖蛋白，IL-16能诱导CD4^ 淋巴细胞，单核细胞及嗜酸性细胞迁移。诱导人CD4^ 淋巴细胞和单核细胞的IL-2R表达，抑制混合淋巴细胞反应，抑制免疫缺陷病毒-1（HIV-1）的复制。     

IL-21——一种新的免疫系统调节因子

IL-21是于2000年发现的属于IL-2细胞因子家族的新成员.它同该家族其它成员(IL-2、IL-4、IL-7、IL-9、IL-13和IL-15)共用一个受体亚单位γc.IL-21由活化的CD4+T辅助细胞产生的,其受体表达在多种免疫细胞(B、T、NK细胞)上,因此对多种免疫细胞有重要的生物调节作用.IL-21能提高B淋巴细胞的增殖,提高IgG1的产生,抑制IgE的产生,从而调节人体体液免疫.IL-21还可增强NK细胞、T淋巴细胞的增殖与杀伤功能,从而增强人体的细胞免疫.作为最新的免疫系统调节因子,IL-21在免疫调节、抗肿瘤中的作用越来越受到研究者的重视,已成为该领域的研究热点.     

Interleukin 21: a key player in lymphocyte maturation

The common gamma chain family of cytokine receptors plays a plethora of roles during the early development, activation, and terminal differentiation of the lymphocyte lineages. The most recently identified member of this family, the IL-21R, is expressed to varying degrees on B, T lymphocytes, and natural killer (NK) cells, whereas IL-21, is reportedly only produced by activated CD4+ T cells. In keeping with this expression pattern the IL-21:IL-21R interaction is important for the latter stages and function of all three lymphoid lineages. IL-21 is a regulator of A-cell differentiation to plasma cells as well as immunoglobulin class switching. In contrast, within the T-cell lineage, IL-21 acts as a co-stimulator of proliferation, enhances memory response, and modulates homeostasis. Within the innate immune system IL-21 has a role in the terminal differentiation of NK cells, enhancing cytotoxic function while also decreasing cellular viability. These immune maturation and stimulating functions have resulted in IL-21 being tested in a variety of models of immunity. In these contexts, IL-21 has shown very promising efficacy in a number of antitumor immune responses mediated by NK and or T lymphocytes.     

Comparison of Biological and Immunological Activities of Human Monocyte-Derived Interleukin 1β and Human Recombinant Interleukin 1β

Recombinant human interleukin 1 beta (rhIL-1 beta) and supernatants of Escherichia coli lipopolysaccharides-stimulated human monocyte (Mo) cultures, containing native human IL-1 beta (nhIL-1 beta), demonstrate significant differences when tested in the mouse co-stimulatory thymocyte (lymphocyte activating factor [LAF]) assay. The aims of the present study were to investigate this characteristic difference between rhIL-1 beta and Mo culture supernatants (Mo supernatants), and to compare the biological and the immunological activity of preparations of rhIL-1 beta and nhIL-1 beta during each step of an identical purification procedure. The biological activity of rhIL-1 beta/nhIL-1 beta preparations was characterized by the use of the LAF assay and the rat islet insulin release assay. An IL-1 beta enzyme-linked immunosorbent assay (ELISA) was established in order to compare the biological and immunological responses of the IL-1 beta preparations. We report that the significant difference between rhIL-1 beta and supernatants of Mo cultures, which was only demonstrable in the LAF assay, is due to the presence of interleukin 6 (IL-6) in the Mo supernatants. We describe a simple cation exchange chromatography separating nhIL-1 beta and IL-6 of Mo supernatants. The highly purified rhIL-1 beta possessing the correct amino-terminal sequence and nhIL-1 beta have identical biological and immunological activities demonstrating a specific biological activity (SBA) of 3 x 10(2) U/ng IL-1 beta. Thus, we have no indications of secondary or tertiary structural differences between rhIL-1 beta and purified nhIL-1 beta. In contrast, both in the LAF assay and in the rat islet insulin release assay the SBA of an amino-extended rhIL-1 beta form, Met-Glu-Ala-Glu-rhIL-1 beta, was only 1-2% of the SBA of rhIL-1 beta, suggesting that structural changes were introduced into the molecule by the amino-terminal extension. In the present study we have demonstrated that systematic combined testing of IL-1 beta preparations in two different biological assays and an immunological assay is useful for the characterization and comparison of the activity of recombinant and native IL-1 beta preparations purified by the use of exactly the same procedures.     

Interleukin (IL)-21 promotes intestinal IgA response to microbiota

Commensal microbiota-specific T helper type 17 (Th17) cells are enriched in the intestines, which can convert into T follicular helper (Tfh) in Peyer's patches, and are crucial for production of intestinal immunoglobulin A (IgA) against microbiota; however, the role of Th17 and Tfh cytokines in regulating the mucosal IgA response to enteric microbiota is still not completely known. In this study, we found that intestinal IgA was impaired in mice deficient in interleukin (IL)-17 or IL-21 signaling. IL-21, but not IL-17, is able to augment B-cell differentiation to IgA⁺ cells as mediated by transforming growth factor β1 (TGFβ1) and accelerate IgA class switch recombination (CSR). IL-21 and retinoic acid (RA) induce IgA⁺ B-cell development and IgA production and drives autocrine TGFβ1 production to initiate IgA CSR. Repletion of T-cell-deficient TCRβxδ^−/− mice with Th17 cells specific for commensal bacterial antigen increased the levels of IgA⁺ B cells and IgA production in the intestine, which was blocked by neutralizing IL-21. Thus IL-21 functions to strongly augment IgA production under intestinal environment. Furthermore, IL-21 promotes intestinal B-cell homing through α₄β₇ expression, alone or with TGFβ and RA. Together, IL-21 from microbiota-specific Th17 and/or Tfh cells contributes to robust intestinal IgA levels by enhancing IgA⁺ CSR, IgA production and B-cell trafficking into the intestine.     

Interleukin 21: a cytokine/cytokine receptor system that has come of age

Interleukin-21 (IL-21) and its receptor represent the sixth cytokine system whose actions were recognized to require the common cytokine receptor gamma chain. IL-21 is produced by activated CD4+ T cells, natural killer T cells, and follicular T helper cells and has actions on a range of lymphohematopoietic lineages. Among its many effects, IL-21 serves a critical role for immunoglobulin production and terminal B cell differentiation, acts as a T cell comitogen and can drive the expansion of CD8+ T cells, can negatively regulate dendritic cell function and plays an essential role in the differentiation of Th17 cells. Importantly, IL-21 is implicated in the pathogenesis of autoimmunity and exhibits potent actions as an antitumor agent. The ability to regulate and manipulate the actions of IL-21, therefore, has important implications for immunoregulation and the therapy of human disease.     

CD21/CR2的研究进展

补体Ⅱ型受体CD21/CR2是B淋巴细胞膜表面C3d/iC3b受体,在免疫应答中起重要的作用。同时人CD21/CR2也是EB病毒膜表面糖蛋白gp350/gp220、HIV-1等的受体,CD21/CR2以不同的结构域与这些配体结合,表现出多种生物学特性。弄清CD21/CR2的结构和功能,可以指导基础免疫研究,也可明确临床许多疾病的发病机理和治疗方向。     

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.