Characterization of T cell epitopes in αs1-casein in cow''s milk allergic, atopic and non-atopic children

BACKGROUND: One to two percent of infants suffer from IgE-mediated allergic reactions against cow's milk proteins. Most children develop clinical tolerance, but approximately 15% are still allergic by the age of 10 years. Little is known about the T cell epitopes in individual cow's milk protein in relation to allergy and tolerance. OBJECTIVE: To identify T cell epitopes in alphas1-casein, the most abundant milk protein, and to investigate T cell responses toward these epitopes in allergic, atopic and non-atopic children. METHODS: Allergen-specific T cell lines (TCLs) were derived from peripheral blood mononuclear cells of 11 cow's milk allergic, nine atopic and nine non-atopic children. T cell responses were measured to alphas1-casein and to overlapping peptides (18-mers), spanning the alphas1-casein molecule. Proliferation was determined by incorporation of (3)H-thymidine, and cytokine production (IL-10, IL-13 and IFN-gamma) was measured by ELISA. RESULTS: Four main regions (amino acid (AA) residues 43-66, 73-96, 91-114 and 127-180) in the alphas1-casein molecule were immunogenic to T cells, among which the AA residues 133-156 spanned the immunodominant part. Only subtle differences were found in peptide recognition between the subject groups. Some of the peptides induced slightly Th1- or Th2-skewed cytokine responses. The increased levels of IL-10 in response to alphas1-casein observed in TCLs from atopic children appeared not to be linked to recognition of specific IL-10-inducing epitopes. CONCLUSIONS: The immunodominant sequence in alphas1-casein is spanned by AA residues 133-156. Tolerance towards alphas1-casein in atopic children may be mediated by an overall induction of IL-10 and not by recognition of certain T cell epitopes. The identified T cell epitopes in children with cow's milk allergy may be useful targets in developing peptide immunotherapy.     

Pseudo-Oversensing of the T Wave by an Implantable Cardioverter Defibrillator: A Nonclinical Problem

Two patients are described who had pseudo-oversensing of T waves during follow-up testing of the Medtronic PCD. Each patient exhibited appropriate T wave sensing following closely coupled spontaneous QRS complexes to subthreshold stimuli without having T wave sensing following sensed or paced complexes. One patient also revealed T wave sensing following fusion beats. The occurrence of T wave sensing in these unique clinical situations was due to the auto-adjusting sensitivity threshold function used by the PCD. Recognition of this normal sensing function will prevent inappropriate reprogramming of the sensitivity or postpace refractory period, interventions that could potentially lead to ventricular tachyarrhythmia undersensing.     

Development of mucosal immune function in man: potential for Gl disease states

The human mucosal immune system is structurally mature and has all the necessary cellular components to generate an immune response at birth. However, in the absence of dietary antigens and bacterial flora, there are no secondary follicles in the Peyer's patches and virtually no immunoglobulin A plasma cells in the lamina propria. Reactive follicle centers develop after birth but it takes 2 years for mucosal IgA plasma cell density to reach adult levels. T cells are present in the epithelium and lamina propria at birth, albeit at a lower frequency than later in life and there are major differences in phenotype between T cells in fetal intestine and postnatal intestine. There is no information on the impact of the massive antigenic challenge at birth on the mucosal immune system. Well-documented deficiencies in the ability of the blood T cells of the neonate to produce interleukin-4 and interferon-gamma may also occur in the intestine. It is still an open question whether it is better to try to prevent immunological sensitization of the newborn by avoiding potential allergens (i.e. cow's milk), or whether early exposure (as happens when premature infants are given formula feeds) might tolerize the infant. Hydrolysed cow's milk formulae are probably less antigenic than whole cow's milk and have been widely used in the treatment of cow's milk allergy. Some thought is now being given as to whether the prophylactic use of hydrolysates can reduce cow's milk allergy in ‘at-risk’ infants.     

红毛五加多糖对机体免疫功能的影响

本文研究红毛五加多糖成分对机体免疫功能的影响,实验结果表明红毛五加多糖可激发T、B-淋巴细胞的生物学效益。     

Phenotype of endomyocardial biopsy-derived T-lymphocyte cultures and chronic rejection after heart transplantation

Chronic rejection (CR) is a major problem in long-term survival in heart transplantation. We analysed whether the occurrence of CR correlates with the incidence of acute rejections (AR) or with characteristics of endomyocardial biopsy-derived cell cultures. CR was diagnosed by annual angiography and defined as all coronary vascular changes. One year after transplantation 24 of the 63 patients had CR (38%). The incidence of AR in CR + and CR — patients was comparable. The patients in both groups had similar individual median percentages of EMB-yielding cell cultures. During the first year the CR — patients had more cultures in which at least 60% of the cells were CD4 + T cells (50% vs 37%, P = 0.05), due to a stronger CD4 predominance in the first 6 months. In the second year the CD4 predominance in the patients diagnosed as CR + after 1 year tended to be higher (P = 0.08). The patients had comparable percentages of cultures predominated by CD8 + T cells, γδ T cells or NK cells, irrespective of the time interval. These results might indicate that CD4 + T lymphocytes play a dual role in the aetiology of CR.     

CD4+CD25+ regulatory T cells: I. Phenotype and physiology

The immune system protects us against foreign pathogens. However, if fine discrimination between self and non-self is not carried out properly, immunological attacks against self may be launched leading to autoimmune diseases, estimated to afflict up to 5% of the population. During the last decade it has become increasingly clear that regulatory CD4⁺CD25⁺ T cells (T_reg cells) play an important role in the maintenance of immunological self-tolerance, and that this cell subset exerts its function by suppressing the proliferation or function of autoreactive T cells. Based on human and murine observations, this review presents a characterization of the phenotype and functions of the Treg cells in vitro and in vivo . An overview of the surface molecules associated with and the cytokines produced by the Treg cells is given and the origin, activation requirements and mode of action of the Treg cells are discussed. Finally, we address the possibility that Treg cells may play a central role in immune homeostasis, regulating not only autoimmune responses, but also immune responses toward foreign antigens.     

The hevein domain of the major latex-glove allergen Hev b 6.01 contains dominant T cell reactive sites

BACKGROUND: Sensitization to natural rubber latex (Hevea brasiliensis) is a major cause of occupational asthma and rhinitis affecting frequent latex-glove users. Hev b 6.01, a known major latex allergen, is cleaved naturally into hevein (4.7 kDa) and a C-terminal fragment (14 kDa). Hevein is an abundant protein in latex-glove extracts. As the immune response to allergens is initiated by activation of allergen-specific CD4(+) T cells, identification of dominant T cell epitopes is crucial for the development of specific immunotherapy. OBJECTIVE: To identify dominant T cell epitopes of Hev b 6.01 in latex-allergic glove users. METHODS: Ten latex-allergic frequent glove users and six non-latex-allergic atopic control subjects were selected, based on clinical symptoms and positive latex-specific serum IgE. Serum IgE reactivity to glove extract and recombinant Hev b 6.01 (rHev b 6.01) were analysed by ELISA. Latex-specific short-term oligoclonal T cell lines were generated from peripheral blood of latex-allergic subjects. These lines were tested for proliferative responses to overlapping 20-mer peptides of the Hev b 6.01 molecule. CD4(+) T cell intracellular cytokines, IL-4 and IFN-gamma were assessed following stimulation with immobilized anti-CD3 in the presence of IL-2. RESULTS: All ten of the latex-allergic patients showed serum IgE binding to glove extract while eight of these also showed IgE binding to rHev b 6.01 by ELISA. Western blotting confirmed reactivity with rHev b 6.01 at around 20 kDa. T cell proliferation assays showed that latex-specific T cell lines from all subjects responded to one or more peptides, with greatest frequency of reactivity to peptides Hev b 6.01 p(10-29) and Hev b 6.01 p(19-38) in the hevein domain. An allergic-type cytokine profile with considerable IL-4 in addition to IFN-gamma was evident from intracellular cytokine staining. CONCLUSION: Hevein is an important T cell as well as B cell immunogen and contains dominant T cell reactive sites.     

CO中毒致迟发性脑病大鼠脑内CD4+T淋巴细胞浸润及神经胶质酸性蛋白的表达

目的观察CO中毒致迟发性脑病（DNS）大鼠脑内CD4^＋T淋巴细胞浸润以及神经胶质酸性蛋白（GFAP）的表达情况，探讨CO中毒致DNS的病理过程。方法25只SD雄性大鼠随机分为对照组、染毒后3、7、10、20d组，每组5只。采用HE和免疫组织化学染色方法，观察染毒后各时间点大鼠脑内病理形态学变化，及CD4^＋T淋巴细胞浸润和GFAP的表达情况。结果HE染色结果显示：各染毒组在大脑皮层及海马均出现神经细胞不同程度的变性、坏死，染毒后7d组最重。免疫组织化学染色结果显示：对照组无CD4^＋T淋巴细胞浸润，有少量GFAP表达；各染毒组不同脑区CD4^＋T淋巴细胞、GFAP均有不同程度的浸润和表达。CD4^＋T淋巴细胞染毒后3d开始浸润，7d达峰值，两者在数量上差异有统计学意义（P〈0．01）。各组染毒后GFAP均有大量表达，随染毒时间延长表达数量呈上升趋势。结论CD4^＋T淋巴细胞可能参与了CO中毒致DNS的免疫病理过程，GFAP阳性细胞对CO中毒引发的DNS可能具有保护作用。     

猕猴组织工程化骨异体植入修复骨缺损T淋巴细胞亚群的检测

目的　通过对T淋巴细胞亚群的检测 ,从免疫学方面探讨同种异体细胞来源的组织工程化骨植入猕猴体内修复长段骨缺损的可行性。方法　用骨髓基质干细胞 (MSCs)经诱导分化为成骨样细胞后与生物衍生骨材料复合培养 ,体外构建组织工程化骨 ,植入 15只异体猕猴体内桥接桡骨 2 .5cm节段骨缺损作为实验组 ;用单纯生物衍生骨材料桥接对侧同样大小骨缺损作为对照组 ;分别于术后 1、2、3、6、12周抽取静脉血和作双侧局部组织取材 ,样本应用流式细胞术检测T淋巴细胞亚群CD3 /CD4 /CD45 、CD3 /CD8 /CD45 和CD2 8 阳性率。结果　术后第 1、2、3、6、12周实验组和对照组T淋巴细胞亚群CD3 /CD4 /CD45 、CD3 /CD8 /CD45 和CD2 8 阳性率两者差异均无显著性 (P >0 .0 5 )。结论　生物衍生骨材料和猕猴MSCs复合构建组织工程化骨植入异体猕猴体内其术后 12周内免疫反应水平低 ,可用以修复猕猴节段骨缺损。