胸腺基质淋巴细胞生成素在呼吸道感染中的作用

胸腺基质淋巴细胞生成素(TSLP)是一个上皮细胞来源的细胞因子,对树突状细胞的极化和Th2细胞因子的产生有极其重要的影响.在T细胞受体活化和Th2细胞因子产生过程中,TSLP也直接促进T细胞增殖.研究发现,TSLP对呼吸道感染和非特异性炎症过程有广泛的免疫调节作用.     

胸腺基质淋巴生成素对肺部2型淋巴细胞的致敏作用研究进展

胸腺基质淋巴生成素(thymic stromal lymphopoietin,TSLP)可通过直接作用和间接作用两种途径在肺部增强2型T辅助(type 2 T helper,Th2)细胞和2型先天淋巴细胞(type 2 innate lymphocytes,ILC2s)分泌2型细胞因子。在间接作用方面,TSLP可利用树...     

胸腺基质淋巴细胞生成素与支气管哮喘的研究进展

胸腺基质淋巴细胞生成素(TSLP)是一种来源于上皮细胞的新型细胞因子.它通过诱导CD11+树突细胞表达协同刺激分子CD40、CD80,促进树突细胞产生招募辅助T细胞2的趋化凶子--胸腺和活化调节的趋化因子和巨噬细胞来源的趋化因子,增强原始CD4+T细胞产生前炎症因子.同时.TSLP可以协同白细胞介素(IL)-1、肿瘤坏死因子增强肥大细胞释放大量辅助T细胞2细胞因子(IL-5、6、8、13.粒-巨噬细胞集落刺激因子,IL-8)的能力,从而诱发无T细胞参与的过敏反应.因此,TSLP)作为过敏反应的始动因子在哮喘发病中发挥重要作用.     

卡介苗对哮喘患儿细胞免疫调节的研究进展

卡介苗使树突细胞正调节CD40、CD80、Ⅱ类分子等表面分子的表达,并使活化的T细胞分泌γ干扰素;使辅助T细胞Th1产生增多而Th2分泌减少,诱导Th1型免疫反应,抑制Th2型免疫应答,纠正Th1/Th2的失衡;显著抑制γδT细胞活性,使γ干扰素增高,而白细胞介素-4下降;能上调CD4+ CD25+ 调节性T细胞的表面Toll样受体表达,促进其增殖,发挥其调抑功能;促使T细胞活化抑制和凋亡,发挥负向免疫调节作用;抑制GATA-3表达,减少Th2型细胞因子生成;抑制哮喘状态下巨噬细胞集落刺激因子的表达,调节气道巨噬细胞的功能,促使巨噬细胞产生的Th1类细胞因子增多,提高Th1免疫应答,纠正Th1/Th2的失衡.卡介苗可以通过多种机制干预哮喘的发病,为哮喘的治疗提供新的思路.     

Th1/Th2免疫应答失衡及其影响因素

辅助性T细胞(Th)1和2可分泌不同的细胞因子,具有不同的免疫功能,且二者的功能相互调节,处于一种平衡状态。母孕期的细胞因子向Th2型偏倚,以维持妊娠;孕母的营养,过敏都会改变胎儿的Th1/Th2平衡状态;胎儿出生后,随着接触不同的抗原,其免疫发育有其自身的特点。细胞因子对Th细胞的分化起着基本的调节作用;树突细胞、调节性T细胞等通过细胞因子网络影响Th1/Th2的平衡。该文就此作一综述。     

特发性血小板减少性紫癜免疫紊乱状态的研究进展

特发性血小板减少性紫癜(ITP)是一种自身免疫性疾病,其病因和发病机制尚未完全明确.目前研究认为与免疫紊乱密切相关:急性期呈辅助T细胞(Th)1优势分化、缓解期呈Th2优势分化;CD4+T细胞是机体的重要调节细胞,在转录因子T-bet/GATA3的作用下,其激活后选择性地优势分化为Th1/Th2,通过分泌特征性细胞因子而发挥免疫作用;也有研究认为,ITP患儿自身反应性T细胞凋亡受到抑制,引起自身反应性T细胞克隆积聚,不断刺激B细胞产生自身抗体并激活细胞毒性T细胞,导致血小板持续破坏.     

Th17细胞研究进展

Th17细胞是一类新型CD4＋T细胞,它与Th1、Th2、调节性T细胞一起构成了CD4＋T细胞的4个主要亚群。Th17细胞的分化过程需要IL-6和转化生长因子-β、转录因子孤独核受体γt及信号传导和转录激活子3等参与,这一分化过程在细胞和分子水平都受到精细的调节。Th17细胞分泌IL-17、IL-22、IL-6等多种细胞因子,在自身免疫性疾病、感染性疾病和移植排斥中发挥着重要作用。因此,Th17细胞及相关细胞因子可能为此类疾病的治疗提供新的靶点和途径。     

慢性丙型肝炎辅助T细胞相关细胞因子与干扰素疗效关系的研究

宿主的免疫状态与慢性丙型肝炎患者病程进展和干扰素治疗疗效密切相关.细胞免疫应答在丙型肝炎的发病机制中起主要作用.机体对丙型肝炎病毒的清除主要依靠细胞毒性T细胞,而细胞毒性T细胞必须在辅助T细胞(Th)的辅佐下才能充分发挥作用.Th1/Th2通过分泌细胞因子来调节细胞免疫和体液免疫,并与抗原呈递细胞如树突细胞、巨噬细胞等分泌的Th调节因子白细胞介素-1、12、18等共同作用,影响丙型肝炎病毒的清除、组织损伤和慢性化过程以及干扰素的治疗效果.     

慢性丙型肝炎辅助T细胞相关细胞因子与干扰素疗效关系的研究

宿主的免疫状态与慢性丙型肝炎患者病程进展和干扰素治疗疗效密切相关.细胞免疫应答在丙型肝炎的发病机制中起主要作用.机体对丙型肝炎病毒的清除主要依靠细胞毒性T细胞,而细胞毒性T细胞必须在辅助T细胞(Th)的辅佐下才能充分发挥作用.Th1/Th2通过分泌细胞因子来调节细胞免疫和体液免疫,并与抗原呈递细胞如树突细胞、巨噬细胞等分泌的Th调节因子白细胞介素-1、12、18等共同作用,影响丙型肝炎病毒的清除、组织损伤和慢性化过程以及干扰素的治疗效果.     

Th17细胞与哮喘的研究进展

支气管哮喘是一种慢性炎症性气道疾病,以往认为辅助性T细胞1 (Th1) /Th2比例失衡是哮喘发病的重要机制.近年发现了一种以产生IL-17为主要细胞因子的Th17细胞,在哮喘的发病机制中具有重要作用,IL-17还具有对哮喘的负性调节作用,有可能成为治疗哮喘的有意义的靶目标.     

Gene expression profiles of peripheral and cord blood mononuclear cells altered by thymic stromal lymphopoietin

Thymic stromal lymphopoietin (TSLP) was reported to induce dendritic cells to produce Th2-attracting chemokines, followed by allergic inflammation through stimulating not only CD4-positive T cells but also CD8-positive T cells. Therefore, in this experiment, GeneChip and hierarchical clustering were applied to screen the molecules in whole immunity triggered by TSLP directly and indirectly using both adult peripheral and cord blood mononuclear cells as well as isolated monocytes. Gene expression profiles screened a variety of molecules that are triggered by TSLP with or without CD40 ligation. In the profile, RNA expressions of indoleamine 2,3-dioxygenase, that is known to induce anergy of T cells and natural killer cells in protecting fetal rejection; many kinds of proteasomes that were reported to trigger cytokine production by inhibiting suppressors of NF-kappaB; and several kinds of chemokines increased, whereas RNA expression of superoxide dismutase 1 decreased, which was unexpected but considered worthy of notice. Expression of chemokines at protein levels and enzymatic activity of indoleamine 2,3-dioxygenase was further confirmed to increase in the presence of TSLP using ELISA and HPLC, respectively. These results suggest that the advent of microarray technology may enable us to screen novel molecular targets to treat TSLP-related allergic inflammation.     

Disruption in cytokine and chemokine production by T-cells in vertically HIV-1-infected children

This study measured cytokine production by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) from 55 human immunodeficiency virus (HIV)-infected children born to HIV-infected mothers, and compared it with vertically exposed but uninfected age-matched children. A significant defect was observed in Th1 cytokine production [interferon-gamma and interleukin-2 (IL-2)] in HIV-infected children compared with controls, but without a concomitant increase in Th2 cytokines. Indeed, IL-5 and IL-10 production was even lower in HIV-infected children than in controls, with the decrease in IL-5 being the best predictive marker of immunodeficiency. In addition, an increased release of tumour necrosis factor-alpha (TNF-alpha) that correlated well with CD4+ levels, and a positive correlation of the TNF-alpha/IL-10 ratio with disease progression was observed. A correlation between AIDS-free status and higher %CD4+ and %CD8+ T-lymphocytes and RANTES (regulated on activation, normal T-cell expressed and secreted) production was also found. Conclusion: A dysfunctional cytokine production of PBMCs was observed in HIV-infected children in both Th1 and Th2 cytokines due to quantitative and qualitative defects induced by HIV-1. An important observation was an increased RANTES production associated with viral isolates of NSI/R5 phenotype and S/L kinetics.     

Cytokine production, activation marker, and skin homing receptor in children with atopic dermatitis and bronchial asthma

T cells are known to develop a critical role in the pathogenesis of atopic dermatitis (AD) and bronchial asthma. T cells involved in AD express the skin homing receptor CLA, but no lung homing receptor has been identified in bronchial asthma. We compared different cell markers and the cytokine production in T cells from children with AD or bronchial asthma. We studied the involvement of CLA+ and CLA- T-cell subpopulations in these diseases. We studied 20 children with acute AD lesions, 15 with mild persistent asthma, and 15 non-atopic controls. All patients were sensitized to house dust mite (DP) and evaluated during the acute phase. Total and specific IgE were measured by immunoassay and the expression of different cell markers and the cytokine production was analyzed by flow cytometry in peripheral blood mononuclear cells. Total IgE was significantly higher in AD children and IgE to DP in the asthmatic children. There was a significant increase in CD25+ CD4+ cells in asthmatic children and in HLA-DR+ CD4+ and HLA-DR+ CD8+ cells in AD. In the CD4+ subsets, there was an increase in IL-13, IL-5 and TNF-alpha in AD compared to controls, a decrease in IFN-gamma in asthmatic children compared to controls, and an increase in IL-13, IL5, IL2, TNF-alpha, and IFN-gamma in the AD compared to asthmatic children. Changes in cytokine production were mainly detected in CLA+ cells in AD and in CLA- cells in asthma. Differences exist in total and specific IgE, activation markers, and cytokine patterns between AD children and children with asthma, with the former expressing a Th2 pattern whereas in asthmatic children we only detected a decrease in IFN-gamma. Moreover, the subpopulations (CLA+ vs. CLA-) expressing these changes were different, indicating that the underlying mechanisms in the two diseases are not exactly the same.     

Human milk--derived oligosaccharides and plant-derived oligosaccharides stimulate cytokine production of cord blood T-cells in vitro

Human milk contains large amounts of free oligosaccharides (HMOs). HMOs have been shown to exert antiinflammatory properties, and evidence for their immunomodulatory effects is increasing. The purpose of this study was to evaluate influences of two human breast milk-derived oligosaccharide samples (neutral and acidic oligosaccharides), and of a low-molecular-weight fucoidan on cytokine production and activation of cord blood mononuclear cells. Cord blood mononuclear cells from randomly chosen healthy newborns were co-cultured with the oligosaccharide samples. By means of flow cytometry, intracellular cytokine production (d 20) and surface marker expression of T cells (d 5) were measured. In vitro-induced Ig levels were quantified nephelometrically (total IgG1) and by ELISA (total IgE) in the supernatant of cell cultures. The acidic oligosaccharide fraction increased the percentage of interferon-gamma producing CD3+CD4+ and CD3+CD8+ cells (p < 0.05) and the IL-13 production in CD3+CD8+ cells (p < 0.05). In acidic oligosaccharide cultures, CD25+ expression on CD3+CD4+ cells was significantly elevated (p < 0.05). Low-molecular-weight fucoidan induced IL-4 production in CD3+CD4+ T cells (p < 0.05) and IL-13 production in CD3+CD8+ T cells (p < 0.05), whereas interferon-gamma production remained unaffected in both T-cell populations. Ig production (total IgE and total IgG1) remained unaffected. Human milk-derived oligosaccharides and plant-derived oligosaccharides affect the cytokine production and activation of cord blood derived T cells in vitro. Therefore, oligosaccharides and, in particular, acidic oligosaccharides may influence lymphocyte maturation in breast-fed newborns.     

Clinical improvement and normalized Th1 cytokine profile in early and long-term interferon-α treatment in a suspected case of hyper-IgE syndrome

We are reporting on a 7-months-old boy with suspected hyper-IgE syndrome, presenting with a therapy resistant severe eczema and an overall reduction of in vitro cytokine production. Interferon-α (IFN-α) treatment resulted in a marked and stable clinical improvement and normalization of in vitro T-cell cytokine production, indicating a valid therapeutic potential of IFN-α as immunomodulating drug.     

T-cell proliferative responses following sepsis in neonatal rats

Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment of animals with COX-2 inhibitor also significantly prevented the sepsis-associated mortality in neonates. In conclusion, the present study demonstrated T-cell suppression during neonatal sepsis is accompanied by a decrease in IL-2 production. Such suppressions were ameliorated with COX-2 inhibitor suggesting a role for PGE2 in the suppressed T-cell-mediated immune function in neonatal sepsis.     

Peripheral blood immune response elicited by beta-lactoglobulin in childhood cow's milk allergy

Several studies analyzing the immune responses in patients with cow's milk allergy (CMA) have used T-cell lines or T-cell clones that require prolonged in vitro cell culturing and may result in a switched cell phenotype and function. We investigated immune responses to beta-lactoglobulin (b-LG) in peripheral blood mononuclear cells after a short in vitro antigen stimulation in children with acute CMA (both IgE-mediated and non-IgE-mediated forms) and in those who outgrew an IgE-mediated CMA. Healthy controls were also investigated. Peripheral blood mononuclear cells were assayed for IL-13, IFN-γ, IL-4, and IL-10. Although b-LG induced a cytokine production and/or cell proliferation almost in all children, included healthy controls, differences were observed among the four groups. Children with IgE-mediated CMA had a marked Th2-response, with high IL-13 production and proliferation, but low IFN-γ; by contrast, children with non-IgE-mediated CMA produced no, or very low, IL-13 and cell proliferation. Children, who outgrew CMA, showed a shift to a Th1-response, with reduced IL-13 and increased IFN-γ. IL-10-responses were high in all groups, with the highest level in healthy children; by contrast, IL-4 was undetectable in all children. This study highlights the use of shortly stimulated peripheral blood cells to investigate the food-induced immune responses.     

Peripheral blood intracellular cytokine analysis in children newly diagnosed with inflammatory bowel disease

Patterns of cytokine profiles have emerged for different forms of inflammatory bowel disease with a predominance of type 1 cytokines in patients with Crohn disease and type 2 cytokine expression in patients with ulcerative colitis. Most of these studies have involved older patients with long-standing disease or after various therapeutic interventions, and patterns of cytokine expression were hypothesized to be influenced by these factors. To evaluate for these possibilities, we studied 23 patients (15 boys) with newly diagnosed Crohn disease (n = 14) or ulcerative colitis. Their mean age at diagnosis was 13.1 +/- 2.9 y (mean +/- SD). Healthy control subjects (n = 9) were previously obtained. Peripheral blood intracellular cytokine analysis was performed within 24 h using a modification of Becton Dickinson's FastImmune Cytokine system. Multiparametric flow cytometry and phenotyping of lymphocytes was performed. T-cell populations were defined as type 1 being CD69(+), CD3(+), and interferon-gamma(+) and type 2 being CD69(+), CD3(+), and IL-4(+). The median percent of type 1 T cells from normal subjects (2.8%) was similar to that of ulcerative colitis subjects (1.8%, p > 0.20) but greater than that of Crohn disease subjects (0.55%, p = 0.05). The median percent of type 2 lymphocytes in normal subjects (1.8%) was greater than that of ulcerative colitis subjects (0.35%, p = 0.02) but was similar to that of Crohn disease subjects (1.1%, p > 0.20). Serial determinations showed the median percent of type 2 T cells increased in ulcerative colitis patients as remission was induced. Reduced activated peripheral type 1 T cells of newly diagnosed, untreated children are similar to interferon-gamma expression in mucosa of adults with postoperative recurrence. Reduced type 2 cytokine expression patterns in subjects with ulcerative colitis are similar to lamina propria T-cell expression levels in adults and improve with disease remission.     

T-cell signal transduction in children with cow's milk allergy – increased MAP kinase activation in patients with acute symptoms of cow's milk allergy

The precise immune mechanisms behind cow's milk allergy (CMA) are still unknown. Previously, the production of the cytokines TNF-α and IFN-γ in T cells from children with CMA has been shown to be decreased, and the production of IL-4 has been shown to be increased when compared to healthy children. As these aberrations in cytokine production may be associated with disturbances in cellular function, we investigated whether T-cell signal transduction is abnormal in children with CMA. For this purpose we evaluated the activation of the MAP kinase Erk2. Thirty-nine infants were included in the study. Of those with CMA, 13 had acute symptoms and 9 were free of symptoms due to a successful elimination diet at the time of the study. To activate T cells and to stimulate MAP kinase phosphorylation, peripheral blood mononuclear cells (PBMC) were incubated with Concanavalin A (ConA). The change in MAP kinase phosphorylation was measured by Western blotting. The increase in MAP kinase phosphorylation after stimulation with ConA for 5 min was significantly higher in cells from patients with acute symptoms of CMA than in cells from CMA patients free of symptoms or cells from healthy children. A time-course experiment showed that the change in MAP kinase phosphorylation was still increasing after 10 min incubation in cells from patients with acute symptoms of CMA. The increased MAP kinase activation was found to correlate positively with non-IgE mediated CMA in patients with acute symptoms of CMA.