Genetic polymorphism and TH1/TH2 orientation

BACKGROUND: It is likely that besides developmental and environmental factors, genetic factors also play an important role in Th1/Th2 orientation and susceptibility to related disorders. Thus, for each genetic factor involved one would expect an opposite pattern of susceptibility towards Th1- and Th2-associated diseases. METHODS: We report a comparative analysis of the pattern of association of four genetic polymorphisms with bronchial asthma (Th2 disease) and Crohn's disease (CD; Th1 disease). The study population included 291 Roman children with bronchial asthma and 72 adult Romans with CD, and haptoglobin, adenosine deaminase (ADA), acid phosphatase locus 1 (ACP1) and MN phenotypes were determined. RESULTS: Compared with controls from the same population, the pattern of phenotype association observed in bronchial asthma is exactly opposite to that observed in CD. The analysis of pairwise gametic type distribution for ACP1, ADA and MN polymorphisms has shown that the pattern of differences between bronchial asthma and controls is opposite to that observed between CD and controls. CONCLUSIONS: The pattern of differences between bronchial asthma versus CD is compatible with the hypothesis that some of the genetic systems considered contribute to Th1/Th2 orientation.     

Biology of human TH1 and TH2 cells

Evidence is accumulating to suggest the existence of polarized human T-cell responses, reminiscent of T_H1 and T_H2 subsets described for mouse T cells. Human T_H1 cells preferentially develop during infections by intracellular bacteria and trigger phagocyte-mediated host defense, whereas T_H2 cells, which predominate during helminthic infestations and in response to common environmental allergens, are responsible for phagocyte-independent host response. Human T_H1 and T_H2 cells exhibit not only different functional properties but probably also distinct surface markers; T_H2, but not T_H1, clones express membrane CD30 and release the soluble form of CD30, a member of the TNF receptor superfamily. The cytokine profile of natural immunity evoked by different offending agents in the context of different host genetic backgrounds appears to be the most critical factor in determining the phenotype of the subsequent specific response. IL-12 and IFN- and produced by macrophages and NK cells favor the development of T_H1 cells, whereas the early production of IL-4 by a stillunidentified cell type favors the development of T_H2 cells. Clearly, polarized human T_H1 and T_H2 responses not only play different roles in protection, they can also promote different immunopathological reactions. Strong and persistent T_H1 responses seen to be involved in organ-specific autoimmunity, contact dermatitis, and some chronic inflammatory disorders of unknown etiology. In contrast, polarized T_H2 responses favor a reduced protection against the majority of infectious agents (including HIV) and, in genetically predisposed hosts, are responsible for triggering of allergic atopic disorders.     

第9、10、11肋间神经和肋下神经的血供

本文观察了25具成人专供研究用的尸体,对50侧第9、10、11肋间神经和肋下神经的血供进行了研究,对该四对神经的营养动脉数目、外径、长度、入神经干部位和来源动脉进行观察测量。发现营养动脉外径较细,长度亦较短,不宜作为肋间神经的血管蒂进行吻合,而肋间神经营养动脉的来源动脉——肋间后动脉,其外径较粗,并有足够长度,作为血管蒂进行吻合较为理想。     

Immunologic influences on allergy and the TH1/TH2 balance

TH2 cell-mediated immune responses against "innocuous" antigens play a triggering role in atopic allergy. Several epidemiologic studies have clearly shown that the reduced microbial exposure of children caused by the westernized lifestyle is responsible for the increased prevalence of allergy that has occurred in the last decades in developed countries ("hygiene hypothesis"). The immunologic changes caused by the reduced exposure to pathogenic and nonpathogenic microbes during childhood are still controversial. The initial interpretation has been a lack of shift of allergen-specific responses from the TH2 to the TH1 phenotype. This is because of reduced production of IL-12 and IFNs by cells of the natural immunity stimulated by bacterial products through their Toll-like receptors (missing immune deviation). Another interpretation emphasizes the importance of reduced activity of T-regulatory cells (reduced immune suppression). However, although there are impressive amounts of data in favor of the missing immune deviation, experimental evidence supporting the role of reduced immune suppression in explaining the increased prevalence of allergy is currently weak or even contradictory. The solution to this question is very important not only from a theoretic point of view but also because of its therapeutic implications.     

Coevolution of TH1, TH2, and TH17 responses during repeated pulmonary exposure to Aspergillus fumigatus conidia

Aspergillus fumigatus, a ubiquitous airborne fungus, can cause invasive infection in immunocompromised individuals but also triggers allergic bronchopulmonary aspergillosis in a subset of otherwise healthy individuals repeatedly exposed to the organism. This study addresses a critical gap in our understanding of the immunoregulation in response to repeated exposure to A. fumigatus conidia. C57BL/6 mice were challenged intranasally with A. fumigatus conidia weekly, and leukocyte composition, activation, and cytokine production were examined after two, four, and eight challenges. Approximately 99% of A. fumigatus conidia were cleared within 24 h after inoculation, and repeated exposure to A. fumigatus conidia did not result in hyphal growth or accumulation of conidia with time. After 2 challenges, there was an early influx of neutrophils and regulatory T (T(reg)) cells into the lungs but minimal inflammation. Repeated exposure promoted sustained expansion of the draining lymph nodes, while the influx of eosinophils and other myeloid cells into the lungs peaked after four exposures and then decreased despite continued A. fumigatus challenges. Goblet cell metaplasia and low-level fibrosis were evident during the response. Repeated exposure to A. fumigatus conidia induced T cell activation in the lungs and the codevelopment by four exposures of T(H)1, T(H)2, and T(H)17 responses in the lungs, which were maintained through eight exposures. Changes in CD4 T cell polarization or T(reg) numbers did not account for the reduction in myeloid cell numbers later in the response, suggesting a non-T-cell regulatory pathway involved in dampening inflammation during repeated exposure to A. fumigatus conidia.     

哮喘患儿激素治疗后TH1/TH2的变化

目的观察哮喘患儿血清中白细胞介素IL12、IL13和IgE水平的变化及糖皮质激素对其的影响。方法采用ELISA法分别检测哮喘患儿急性期及口服强的松5～7天后、健康对照组血清中IL12、IL13和IgE的水平。结果哮喘组患儿IL12水平急性发作期较治疗后和健康对照组低,差异均有显著性（P〈0.01）。IL13水平急性发作期较治疗后和健康对照组高,差异均有显著性（P〈0.01）,IgE水平急性发作期较治疗后和健康对照组高,差异均有显著性（P〈0.01）。直线相关分析表明,血清中IL12与IL13负相关,与IgE呈负相关,IL13与IgE呈正相关。结论哮喘患者血清中IL13、IgE水平升高,IL12水平下降,3者的变化相关,糖皮质激素可使IL13水平下降,IL12水平升高。     

TH1 and TH17 cells promote crescent formation in experimental autoimmune glomerulonephritis

Autoimmunity against the Goodpasture antigen α3IV‐NC1 results in crescentic glomerulonephritis (GN). Both antibodies and T cells directed against α3IV‐NC1 have been implicated in disease development and progression. Using the model of experimental autoimmune glomerulonephritis (EAG) in DBA/1 mice, we aimed to characterize the frequency and function of α3IV‐NC1‐specific CD4⁺ T cells in the kidneys. DBA/1 mice repeatedly immunized with human α3IV‐NC1 developed necrotizing/crescentic GN. Kidneys with crescentic GN contained CD4⁺ cells responding to α3IV‐NC1 with the production of IFN‐γ or IL‐17A, demonstrating the accumulation of both α3IV‐NC1‐specific T_H1 and T_H17 cells. To test the functional relevance of T_H1 and T_H17 cells, EAG was induced in DBA/1 mice deficient in IFN‐γR, IL‐17A or IL‐23p19. Mice of all knockout groups mounted α3IV‐NC1 IgG, developed nephrotic range proteinuria, and IgG deposition to the glomerular basement membranes at levels similar to immunized wild‐type mice. However, all knockout groups showed significantly fewer glomerular crescents and attenuated tubulointerstitial damage. Our results suggest that both α3IV‐NC1‐specific T_H1 and T_H17 cells accumulate in the kidneys and are crucial for the development of necrotizing/crescentic GN. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

恶性淋巴瘤患者TH 1/TH 2细胞因子表达水平的研究

目的 探讨恶性淋巴瘤患者血清中TH1/TH2细胞因子变化及其临床意义,为肿瘤的免疫治疗提供实验依据.方法 用流式细胞小球微阵列术(cytometric bead array,CBA)检测92例恶性淋巴瘤患者及70例健康人群血清中γ干扰素(IFN-γ)、肿瘤坏死因子-α仪(TNF-α)、白细胞介素(IL-2、IL-4、IL-5、IL-10)表达水平.结果 92例恶性淋巴瘤患者血清中TH1型细胞因子的水平分别为:IFN-γ(34.26±33.4g)pg/ml、TNF-α(8.17±10.09)pg/ml、IL-2(3.74 4±1.72)pg/ml;TH2型细胞因子的水平分别为:IL-10(6.28±8.56)pg/ml、IL-5(3.53±3.20)pg/ml、IL-4(6.22±7.13)pg/ml.除TNF-α表达水平降低外,其余5项均明显高于健康体检组,差异有统计学意义(P＜0.01).TH1细胞因子IL-2与TH2细胞因子IL-4的比值明显下降(0.78±O.44),与健康体检组(1.09±0.45)比较差异有统计学意义(P＜0.01).IL-10与疾病的进展相关,Ⅲ/Ⅳ期恶性淋巴瘤患者的表达水平为(9.58±13.96)pg/ml,Ⅰ/Ⅱ期的表达水平为(4.77±3.50)pg/ml,二者比较差异有统计学意义(P＜0.01).IFN-γ在大于60岁的恶性淋巴瘤患者中表达水平明显降低,与其他年龄段恶性淋巴瘤患者比较差异有统计学意义(P ＜0.05).结论 恶性淋巴瘤患者血清中TH1/TH2细胞因子平衡失调,检测TH1/TH2细胞因子可作为评价淋巴瘤临床进展及预后指标.TH1/TH2平衡向TH2方向漂移,这可能是肿瘤细胞发生免疫逃逸,从而导致肿瘤的发生或者转移的原因之一.     

Boswellia carterii Extract Inhibits TH1 Cytokines and Promotes TH2 Cytokines In Vitro

Traditional herbal formulas used to treat inflammatory arthritis in China and India include Boswellia carterii or Boswellia serrata. They both contain boswellic acids (BAs) which have been shown to exhibit anti-inflammatory and antiarthritic properties. This study tests the hypothesis that mixtures of BAs derived from B. carterii have immunomodulatory properties. B. carterii plant resin obtained from China was prepared as an ethanol extract, and the presence of seven BAs was confirmed by column chromatography, high-performance liquid chromatography, and UV laser desorption/ionization tandem mass spectroscopy. The extract was then tested for its ability to alter in vitro production of TH1 cytokines (interleukin-2 [IL-2] and gamma interferon) and TH2 cytokines (IL-4 and IL-10) by murine splenocytes. Delivery of the resin extract using ethanol as a solvent resulted in significant cellular toxicity not seen with the addition of ethanol alone. By contrast, delivery of the resin extract using a sesame oil solvent resulted in a dose-dependent inhibition of TH1 cytokines coupled with a dose-dependent potentiation of TH2 cytokines. These results indicate that a purified mixture of BAs from B. carterii plant resin exhibits carrier-dependent immunomodulatory properties in vitro.     

NDV-ATV治疗对非小细胞肺癌患者外周血TH极化的影响

目的 探讨新城鸡瘟病毒修饰的自体肿瘤疫苗(NDV—ATV)对非小细胞肺癌(NSCLC)患者TH1／TH2的影响。方法 用ELISA方法于手术前2d、NDV—ATV治疗前1周及每次接种后1周检测外周血血清中TH1类细胞因子(IL-2、IFN-7)和TH2类细胞因子(IL-4、IL-10)浓度。结果 NSCLC患者免疫系统以TH2占优势；经连续4次(4周)NDV—ATV治疗后，以TH1占优势。结论 NSCLC患者机体免疫系统以TH2占优势，可能与肿瘤“免疫逃逸”有关；NDV—ATV主动特异性免疫疗法能改变肿瘤患者TH2占优势的局面，使TH2向TH1扭转，这可能是NDV-ATV免疫治疗的机理之一。     

Boswellia carterii extract inhibits TH1 cytokines and promotes TH2 cytokines in vitro

Traditional herbal formulas used to treat inflammatory arthritis in China and India include Boswellia carterii or Boswellia serrata. They both contain boswellic acids (BAs) which have been shown to exhibit anti-inflammatory and antiarthritic properties. This study tests the hypothesis that mixtures of BAs derived from B. carterii have immunomodulatory properties. B. carterii plant resin obtained from China was prepared as an ethanol extract, and the presence of seven BAs was confirmed by column chromatography, high-performance liquid chromatography, and UV laser desorption/ionization tandem mass spectroscopy. The extract was then tested for its ability to alter in vitro production of TH1 cytokines (interleukin-2 [IL-2] and gamma interferon) and TH2 cytokines (IL-4 and IL-10) by murine splenocytes. Delivery of the resin extract using ethanol as a solvent resulted in significant cellular toxicity not seen with the addition of ethanol alone. By contrast, delivery of the resin extract using a sesame oil solvent resulted in a dose-dependent inhibition of TH1 cytokines coupled with a dose-dependent potentiation of TH2 cytokines. These results indicate that a purified mixture of BAs from B. carterii plant resin exhibits carrier-dependent immunomodulatory properties in vitro.     

TH1 AND TH2 RESPONSES IN PATHOGENESIS AND REGULATION OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS

Experimental autoimmune uveoretinitis (EAU) in animals can be induced by immunization with retinal antigens or their fragments and represents human uveitis of putative autoimmune origin. The pathogenesis of EAU, and likely also of human uveitis, involves cell-mediated destruction of retinal tissues that is dependent on retinal antigen-specific T cells. Because in most cases a Th1-type response has been implicated in path ogenesis, the prevailing consensus has been that immunoregulatory manipulations designed to enhance the Th2 response at the expense of the Th1 response will be bene-ficial in clinical treatment of uveitis. This assumption may not always be correct. The present review will summarize the evidence that, despite a central role for Th1 response in uveitis, an unopposed Th2-like response can be equally or more destructive to the retinal tissues. Furthermore, the Th1 response itself triggers regulatory circuits that feed back and dampen further recruitment of antigen-specific T cells into the Th1 effector pool. Thus, although the Th1 effector response can and does result in retinal pathology, immunoregulatory strategies must take into account that immune deviation therapies designed to replace the Th1 with a Th2 response might result in exchanging one type of pathology for another rather than in achieving the desired therapeutic effect.