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Background Selected cytokines produced by allergen specific CD4+ T cells from atopic individuals contribute to both the specific and non-specific effector mechanisms of the allergic immune response. The chemokine family of cytokines and tumour necrosis factor (TNF)-α are leucocyte regulatory and proinflammatory molecules. The chemokines include interleukin (IL)-8 and the RANTES/SIS cytokines. Objective There bas been no systematic survey of chemokine production in T-cell subtypes. Because of their wide range of biological properties, it might be expected that they would be closely regulated by T cells. This paper illustrates one way (through the characterization of T-cell clones) these questions might be addressed. Methods Northern blot analysis was used to quantitate steady state transcription of selected cytokine genes and enzyme linked immunosorbent assay (ELISA) was used to quantitate soluble product. Results mRNA expression of the chemokines (IL-8. HuMIP-lα and HuMIP-lβ) and TNFα is upregulated in TH2-like cloned house dust mite reactive human CD4+ T cells under conditions of activation and during the induction phase of anergy. Although the development of anergy superinduces mRNA for both IL-8 and TNFα, protein production is low compared with that released during activation. In contrast, RANTES, a chemoattractant for CD4+ /CD45RO+ memory T cells, eosinophils and basophils, is constitutively expressed at the RNA level by the T cells and not modulated by signals of activation and anergy induction. The production of IL-2, IL-4 and IL-5 mRNA and proteins during the induction of anergy peaks at 2h after stimulation, whereas the kinetics following activation of the T cells is delayed in comparison. Conclusion These data show that the induction of the anergic state coincides with post-transcriptional regulation of selected cytokine genes. Further study of these phenomena will impact on our understanding of the mechanisms of induction of anergy and the regulation of allergic immune responses in desensitization. [ABSTRACT FROM AUTHOR]

Highlights the papers with implications for allergy and respiratory cellular immunology that are presented during the 7th International Congress of Immunology in Berlin, Germany. Biology of the lower affinity Fc receptor for immunoglobulin E; Interactions between cytokines and endothelial cells; Role of T cell bearing gamm-delta antigen receptors.

This article focuses on the impact of allergen on the airway epithelium. The epithelium has a central position in allergic respiratory disease as both a target for allergen and a route for therapeutic intervention. It also has the potential to modulate disease processes by producing cytokines. Although asthma patients with chronic progressive disease account for only 10-20% of patients, they are severely affected and use a disproportionate share of medical resources. Avoiding or reversing progressive changes in the airway which are likely to result from chronic inflammation and epithelial restitution, remains a significant challenge in asthma therapy.

The author discusses the findings of a study conducted by researcher J. Wisniewski and colleagues on humoral and cellular responses in peanut-allergic (PA) children who received peanut oral immunotherapy. He believes that the study and other mechanistic clinical studies on food allergy play an important role in identifying the aspects of the cellular immune status of patients that distinguishes between desensitization and tolerance induction.

Summary Background Lung-homing of progenitor cells is associated with inflammatory and remodelling changes in asthma. Factors that modulate the increased traffic of progenitor cells to the site of inflammation in asthma remain to be defined. Interleukin ( IL)-4 and IL-13 are Th2 cytokines that are key regulators of asthma pathology. Objective We investigated the role of IL-4 and IL-13 in modulating the trans-migrational responses of haemopoietic progenitor cells ( HPC). Methods HPC were enriched from cord blood ( CB) and peripheral blood ( PB) samples. Migration of HPC was assessed using transwell migration assays, and responding cells were enumerated by flow cytometry. Results IL-4 and IL-13 primed migration of CB- and PB-derived HPC ( CD34+45+ cells) to stromal cell-derived factor-1α ( SDF-1α), in vitro. However, these cytokines had no effect on migrational responses of eosinophil-lineage committed progenitors ( CD34+45+ IL-5Rα+ cells) or mature eosinophils to SDF-1α. For HPC, priming effects of IL-4 (0.1 ng/mL) and IL-13 (0.1 ng/mL) were detectable within 1 h and optimal at 18-h post-incubation, and IL-4 was the more effective priming agent. Pre-incubation with IL-4 or IL-13 had no effect on the intensity of cell surface expression of SDF-1α receptor, CXCR4. Disruption of cell membrane cholesterol content by pre-incubation with polyene antibiotics inhibited IL-4 priming of SDF-1α stimulated migration of HPC indicating that increased incorporation of CXCR4 into membrane lipid rafts mediated the cytokine primed migrational response of HPC. This was confirmed by confocal fluorescent microscopy. Conclusions and Clinical Relevance IL-4 and IL-13 prime the migrational response of HPC to SDF-1α by enhancing the incorporation of CXCR4 into lipid rafts. The priming effect of these cytokines is specific to primitive HPC. These data suggest that increased local production of IL-4 and IL-13 within the lungs may promote increased SDF-1α mediated homing of HPC to the airways in asthma. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is characterized by persistent inflammation of sinonasal mucosa. Glucocorticoid-induced leucine zipper (GILZ) is a recently described anti-inflammatory mediator. Objective Here we analysed the expression of GILZ in CRSsNP and CRSwNP, its association with response to surgery, and its cytokine-driven expression regulation in the upper airways. Methods The messenger RNA (mRNA) and protein expression of GILZ in 33 CRSsNP, 32 CRSwNP, and 11 control samples was assessed by means of a quantitative RT-PCR and immunohistochemistry, respectively. Nasal explant culture was used to investigate the effect of IFN-γ, IL-4, IL-13, IL-1β, and TNF-α on GILZ mRNA expression in normal sinonasal mucosa. Results The GILZ mRNA and protein expression was significantly suppressed in both CRSsNP and CRSwNP patients compared with controls. No significant difference in GILZ expression was found between CRSsNP and CRSwNP patients. Comparing patients responsive and patients recalcitrant to surgery, a significant further decrease of GILZ expression was found in recalcitrant patients both in the CRSsNP and in the CRSwNP group. IL-1β, TNF-α, IL-4, and IL-13 reduced, whereas IFN-γ enhanced GILZ mRNA levels in the sinonasal mucosa. Conclusion Down-regulated expression of GILZ may contribute to the pathogenesis of CRSsNP and CRSwNP and associate with response to surgery. GILZ expression in the upper airways can be regulated differentially by different cytokines. [ABSTRACT FROM AUTHOR]

Background Increased vessel number and permeability are important features of the nasal mucosa in allergic rhinitis (AR), and are mediated in part by the cytokine vascular endothelial growth factor (VEGF). Eosinophils are the major effector cells in the nasal secretions of patients with AR during the responses to allergen challenges. To evaluate the involvement of VEGF in nasal allergic inflammation, we monitored the levels of VEGF, eosinophil cationic protein (ECP), and specific antibodies in the nasal lavage fluids (NLFs) of patients with AR in response to Dermatophagoides pteronyssinus ( Dpt). Methods Sixty-three subjects with sensitization to Dpt were enrolled: 29 patients with AR (group I) who showed positive responses in a nasal provocation test (NPT) with Dpt; and 34 asymptomatic controls (group II) who showed sensitization to Dpt but negative NPT results. NLF samples were collected at baseline, 10, 30, and 60 min, and at 3, 6, and 24 h during the NPT. The ECP levels in the NLF samples were measured using the ImmunoCAP system. VEGF and Dpt-specific IgE, IgA, and IgG in the NLF samples were detected by ELISA. Results The eosinophil counts and ECP levels in the samples were significantly increased in group I, but not in group II, during the early and late responses. Although the baseline VEGF level was not significantly different between groups I and II, increased VEGF production was noted in group I after the NPT, especially during the early response. The level of Dpt-specific IgA was significantly increased in group I during the NPT. A relationship was found between the levels of VEGF and ECP or Dpt-specific IgA in the NLF samples collected at 10 min and at 3–6 h ( P<0.05, respectively). Conclusion Nasal VEGF secretion in response to allergen exposure may augment eosinophilic inflammation in the nasal mucosa of patients with AR. [ABSTRACT FROM AUTHOR]

Background Asthma is a chronic inflammatory disease of the lung and its incidence has been increasing around the world. We previously reported that oral administration of a water-soluble extract prepared from Actinidia arguta, code-named PG102, could modulate the level of Th1 and Th2 cytokines and suppress the production of immunoglobulin E (IgE) in the ovalbumin (OVA)-immunized murine model as well as in the in vitro cell culture system, and furthermore could significantly improve dermatitis conditions in the NC/Nga murine model. These data suggested that PG102 might have therapeutic effects in a broad range of allergic diseases. Objective To assess the possible anti-allergic effects of PG102 in the OVA-induced murine asthma model. Methods The quality of PG102 was standardized, using its effects on the production of IgE, IL-5, and IL-13, in in vitro cell culture systems. To test effects on asthma, BALB/c mice were orally administrated with PG102, followed by OVA sensitization and challenge to induce asthmatic symptoms. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid, serum, and lung tissue were analysed by using various methods. Results PG102 could decrease the level of IgE, IL-5, and IL-13 in in vitro cell culture systems with IC50 being 1.12–1.43 mg/mL. PG102 could ameliorate asthmatic symptoms, including AHR and eosinophilia in the lungs. Such improvement of asthmatic symptoms by PG102 was accompanied by the down-regulation of IL-5 and IgE. In PG102-treated mice, high level expression of heme oxygenase-1, a potent anti-inflammatory enzyme, was observed in alveolar inflammatory cells, while the mRNA levels of foxp3, TGF-β1, and IL-10, important markers for regulatory T cells, were also up-regulated in the lung tissue. Conclusions PG102 may have potential as a safe and effective reagent for the prevention or treatment of asthma. [ABSTRACT FROM AUTHOR]

Background We have successfully generated an IgE-associated (extrinsic/allergic) mouse model of atopic dermatitis in K14-IL-4-Tg/CByB6 mice. The newly described subset of non-IgE-associated (intrinsic/non-allergic) atopic dermatitis in human patients raises the question on the role of IgE in the pathogenesis. Objective The aim of this study was to develop a non-IgE-associated atopic dermatitis model in K14-IL-4-Tg/SKH1 mice. Methods K14-IL-4-Tg/CByB6 mice were crossed with SKH1 mice to produce K14-IL-4-Tg/SKH1 mice. Phenotypes of clinical and histological, cytokine expression in the skin lesions, and total serum IgE in K14-IL-4-Tg/CByB6 and K14-IL-4-Tg/SKH1 mice were compared. The CD40 and CD40L on T and B cells were also studied to differentiate their roles in IgE production. Results K14-IL-4-Tg/SKH1mice had a normal total serum IgE level and manifested a chronic inflammatory skin phenotype identical to that of K14-IL-4-Tg/CByB6 IgE-mediated mice in clinical morphology, histology, infiltration of mononuclear cells/eosinophils/mast cells, mast cell degranulation, and up-regulation of chronic lesional cytokine mRNA expression of IL-1β, IL-3, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, and TNF-β. We also found that the inability of CD4+ T cells of the K14-IL-4-Tg/SKH1mice to up-regulate CD40L expression upon stimulation might account for their inability to up-regulate the IgE level. B cell abnormality was ruled out as CD19+ B cells of K14-IL-4-Tg/SKH1 mice synthesized the same amount of IgE in vitro compared with K14-IL-4-Tg/CByB6 mice in the presence of IL-4 and soluble CD40L. Our studies further suggested that the defect of early growth response-1 in T cells might be responsible for the impaired CD40L up-regulation in K14-IL-4-Tg/SKH1 mice. Conclusion K14-IL-4-Tg/SKH1 mice developed skin inflammation that resembled human intrinsic atopic dermatitis. Therefore, this model may be suitable to study the pathogenesis of intrinsic atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background IL-18 is a proinflammatory cytokine that plays an important role for T-helper type 1 (Th1) and Th2 cytokine in the presence/absence of IL-12. It has been recently shown that human IL-18 plays a role in atopic dermatitis (AD) by enhancing IL-4 and IL-13 production and by stimulating the synthesis of IgE. Objective We wanted to evaluate the associations of single-nucleotide polymorphism (SNP) and the haplotype in the IL-18 gene, hence we performed genotyping for the SNPs in the IL-18 gene in AD patients and normal controls. Method We genotyped three SNPs from the IL-18 gene for the 1120 case–control samples (646 AD patients and 474 normal controls). We measured the serum IL-18, IL-4 and IL-13 concentrations in 74 individuals (25 ADe, 25 ADi and 24 controls) by performing ELISA. Result The rs795467 SNP and haplotype T–T–C were significantly associated with AD, and especially between the ADe and normal control groups ( P=0.03 and 0.01). The serum IL-18 concentration was higher in the AD group than in the normal controls without any correlation with the rs795467 polymorphism. We did not find any correlations between the serum IL-18 levels and the SCORing atopic dermatitis index, the blood eosinophil counts and the ECP, and there was no correlation between the serum IL-18 levels and the serum IL-4 and IL-13 levels. Conclusion We found that the one SNP and the haplotype T–T–C were strongly associated with the allergic type of AD, but not with the non-allergic intrinsic type. These data support the hypothesis that IL-18 up-regulates IgE production, yet more experiments will be needed to prove the in vivo involvement of Th2 cytokine. [ABSTRACT FROM AUTHOR]

Background Hev b 6.01 (prohevein) and Hev b 5 [acidic natural rubber latex (NRL) protein] are major IgE-binding allergens in NRL allergy. Objective To examine allergen-specific cytokine and chemokine responses in NRL-allergic patients. Methods Fourteen NRL-allergic patients and 10 healthy controls participated in the study. Hev b 6.01 and Hev b 5 were purified under non-denaturating conditions by chromatographic methods. Specific IgE antibodies were measured by ELISA and proliferation of peripheral blood mononuclear cells (PBMC) by 3H-thymidine incorporation assay. Allergen-specific induction of cytokine and chemokine mRNA in PBMC was measured by real-time PCR and protein levels by ELISA. Surface expression of chemokine receptors was analysed by flow cytometry. Results Twelve (86%) NRL-allergic patients had positive skin prick test reactions and IgE antibodies against Hev b 6.01, but less than 30% responded to Hev b 5. Cell proliferation against Hev b 6.01, but not against Hev b 5, was significantly increased. Both allergens elicited significantly higher expression of pro-inflammatory and T-helper type 2 cytokines (TNF, IL-12p40, IL-13) and chemokines (CCL3, CCL4, CCL20) in the NRL-allergic patients than in controls. Interestingly, mRNA expression of the regulatory cytokine TGF-β1 was reduced, whereas IL-10 expression was enhanced after allergen stimulations in patients with NRL allergy. Finally, the NRL-allergic patients showed increased CCR4 expression on CD3+CD8− T cells and decreased CXCR3 expression on CD3+CD8+ T cells. Conclusion Allergen-specific induction of cytokines and chemokines in PBMC and chemokine receptor expression on circulating T cells may contribute to the pathogenesis of NRL allergy. [ABSTRACT FROM AUTHOR]

Background Allergen-derived (T cell epitope) peptides may be safer for immunotherapy than native allergen, as they do not cross-link immunoglobulin (Ig)E. However, HLA polymorphism results in multiple potential epitopes. Synthetic peptides of phospholipase (PL) A2 were selected for a peptide vaccine, on the basis of binding affinity for commonly expressed HLA-DR molecules. Objective To evaluate treatment with an HLA-DR-based PLA2 peptide vaccine in subjects with mild honeybee allergy in an open, controlled study. Methods Twelve volunteers with allergy to bee venom received nine intradermal injections of PLA2 peptides, with six untreated subjects serving as controls. Outcome was assessed by the size of the late-phase cutaneous reaction to allergen, peripheral blood mononuclear cell (PBMC) proliferation, cytokine release, and expression of genes associated with immune regulation. Results Subjects receiving peptides showed a decrease in the magnitude of the late-phase cutaneous reaction to bee venom compared with controls ( P=0.03). The proliferation of venom-stimulated PBMCs decreased in treated subjects compared with controls ( P=0.01). Peptide treatment reduced the production of IL-13 by PLA2-stimulated PBMCs ( P<0.01) and IFN-γ ( P<0.01), and increased the production of IL-10 ( P=0.02). Transcription of the suppressor of cytokine signalling ( Socs)3 gene was significantly increased following therapy. A transient, but modest, increase in allergen-specific IgG was also observed. Conclusion HLA-DR-based T cell epitopes modify surrogate markers associated with successful immunotherapy and induction of immune regulation, supporting the concept that this form of treatment may be efficacious in human allergic disease. [ABSTRACT FROM AUTHOR]

Allergic asthma is a complex disorder characterized by local and systemic T helper type 2 -cell responses such as the production of IL-13, a cytokine associated with the induction of airway hyper-responsiveness (AHR), chronic pulmonary eosinophilia, airway mucus overproduction and eosinophilic oesophagitis. Our study aimed to address the therapeutic potential of a human anti-human IL-13 IgG4 monoclonal antibody (CAT-354) in a murine model of respiratory and oesophageal inflammation induced by intratracheal human IL-13. BALB/c mice were treated on days 1 and 3 with CAT-354 (intraperitoneal injection), and human IL-13 was injected intratracheally on days 2 and 4. AHR to methacholine, airway eosinophilia in bronchoalveolar lavage fluid, histologic analysis of goblet cell metaplasia and oesophageal eosinophilia were evaluated. Human IL-13 induced airway eosinophilia and goblet cell metaplasia in mice in a dose-dependent manner. Moreover, intratracheal dosing with 25 μg of human IL-13 was sufficient to induce AHR, goblet cell metaplasia and oesophageal eosinophilia. Pretreatment with CAT-354 significantly reduced AHR, airway eosinophilia and oesophageal eosinophilia. These results demonstrate that anti-human IL-13 (CAT-354) is a potential therapeutic treatment for allergic airway and oesophageal diseases. [ABSTRACT FROM AUTHOR]

The T cell reactivity to the major allergen of bee venom, phospholipase A2, has been thoroughly characterized. In contrast, only little is known about the human cellular response to major allergens from wasp venom.To characterize the human T cell response to antigen 5 fromVespula vulgaris, Ves v 5.Recombinant Ves v 5 was used to establish allergen-specific T cell lines (TCL) and T cell clones (TCC) from the peripheral blood of vespid-allergic and non-allergic individuals. Ves v 5-specific TCL were mapped for T cell epitopes using overlapping synthetic peptides representing the complete amino acid sequence of Ves v 5. Ves v 5-specific TCC were analysed for antigen-induced secretion of IL-4, IFN-γ and IL-10.Seventeen distinct T cell epitopes were recognized by allergic individuals among which Ves v 5181–192 was identified as a dominant T cell epitope. Partially different epitopes were observed in TCL from non-allergic subjects and the dominant epitope Ves v 5181–192 was not prevalent in these cultures. Ves v 5-specific TCC isolated from allergic individuals did not show the typical T helper type 2 (Th2)-like cytokine profile in response to specific stimulation, i.e. high amounts of IL-4 and low IFN-γ. TCC from non-allergic individuals showed a Th1-like cytokine pattern.Our findings provide evidence that the allergic T cell response to Ves v 5 is not Th2-dominated and that different immunogenic sites on this major wasp venom allergen are recognized by allergic and non-allergic individuals. [ABSTRACT FROM AUTHOR]

CD4+CD25+ regulatory T cells suppress proliferation and cytokine production by human T cells both to self-antigens and exogenous antigens. Absence of these cells in human newborns leads to multiple autoimmune and inflammatory disorders together with elevated IgE levels. However, their role in human allergic disease is still unclear. This study aimed to evaluate the capacity of CD4+CD25+ regulatory T cells to suppress proliferation and cytokine production outside and during birch-pollen season in birch-allergic patients relative to non-allergic controls. CD4+ cells were obtained from blood of 13 birch-allergic patients and six non-allergic controls outside pollen season and from 10 birch-allergic patients and 10 non-allergic controls during birch-pollen season. CD25+ and CD25− fractions were purified with magnetic beads and cell fractions, alone or together in various ratios, were cultured with antigen-presenting cells and birch-pollen extract or anti-CD3 antibody. Proliferation and levels of IFN-γ, IL-13, IL-5 and IL-10 were measured by thymidin incorporation and ELISA, respectively. Numbers of CD25+ cells were analysed by flow cytometry. CD4+CD25+ regulatory T cells from both allergics and non-allergics potently suppressed T cell proliferation to birch allergen both outside and during birch-pollen season. However, during season CD4+CD25+ regulatory T cells from allergic patients but not from non-allergic controls were defective in down-regulating birch pollen induced IL-13 and IL-5 production, while their capacity to suppress IFN-γ production was retained. In contrast, outside pollen season the regulatory cells of both allergics and non-allergic controls were able to inhibit T-helper 2 cytokine production. This is the first study to show differential suppression of Th1 and Th2 cytokines, with CD4+CD25+ regulatory T cells from birch-pollen-allergic patients being unable to down-regulate Th2, but not Th1 responses during birch-pollen season. [ABSTRACT FROM AUTHOR]

Breast milk contains many immunomodulatory factors (soluble CD14 (sCD14), IgA and cytokines) with the potential to influence infant immune development. To determine if changes in breast milk ω-3 polyunsaturated fatty acid (n-3 PUFA) composition as a result of maternal dietary fish oil supplementation during pregnancy can modify levels of these immunological parameters in breast milk. In a randomized controlled trial, 83 atopic women received either 4 g fish oil capsules (containing 3.7 g n-3 PUFA) ( n=40) or 4 g olive oil capsules ( n=43) from 20 weeks gestation until delivery. Breast milk was collected 3 days post-partum and fatty acids were analysed by gas liquid chromatography and IgA, sCD14 and cytokines (IL-5, IL-6, IL-10, TNF-α and IFN-γ) were quantitated by ELISA or time resolved fluorescence (TRF). ω-3 docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) levels were significantly higher ( P<0.001) in breast milk from women supplemented with fish oil ( n=33, DHA mean 1.15%, SD 0.47% and EPA mean 0.16%, SD 0.07%) than in samples from the control group ( n=40, DHA mean 0.50%, SD 0.17% and EPA mean 0.05%, SD 0.02%). Breast milk arachidonic acid (AA; 20:4n-6) levels were significantly lower ( P=0.045) in the fish oil group (mean 0.55%, SD 0.12%) compared with the control group (mean 0.61%, SD 0.14%). Breast milk IgA was positively correlated with DHA ( P=0.046) and 22:5n-3 ( P=0.003), but inversely correlated with linoleic acid (LA; 18:2n-6) ( P=0.034). Levels of sCD14 were also positively correlated with 22:5n-3 ( P=0.009). Cytokines involved in IgA synthesis (IL-10 and IL-6) were also significantly correlated with both IgA and n-3 PUFA levels, although there were no differences in the levels of breast milk IgA, sCD14 or cytokines between study groups. Supplementation with fish oil during pregnancy significantly alters early post-partum breast milk fatty acid composition. ω-3 PUFA levels were positively associated with IgA and sCD14 levels, suggesting a relationship between fatty acid status and mucosal immune function. [ABSTRACT FROM AUTHOR]

Background The low affinity receptor for IgE, CD23, has been described in several pathological conditions. However, the factors involved in the upregulation or downregulation of this receptor are still debated. Methods and Results We studied the effect of interleukin 7 (IL 7) on the expression of CD23 in normal PBT cells stimulated with PMA + Ca2. The data indicate that activated PB-T cultured in the presence of IL-7 showed an increased expression of CD23. The induction of IL-7 on CD23 production appears to be independent of IL-2, IL-4, IL-9, IL-15, Indeed, the addition of specific MoAbs anti-IL-2. IL-4. IL-9. IL-15 or anti-IL2R was unable to block the effect of IL-7 on CD23. The addition of IL-7 to a specific subset CD4+CD23+ was able to augment the adhesiveness of T cells to parenchynial cell monalayers. The use of different cytokine (IL-2, IL-4, IL-9, IL-15) resulted in no increase of adhesiveness. In contrast the addition of IL-7 to a different T-cell subset (i.e. CD4+CD23-) was unable to rescue the lack of adhesiveness observed in these cells. Blocking experiments with MHM6 MoAb were able to drastically reduce the adhesiveness observed in CD4+CD23+ subsets. The presence of LFA-1 and VLA-4 adhesion molecules were responsible for the augmented adhesiveness of activated CD4+CD23+ T cells cultured in the presence of IL-7. Blocking experiments with anti-LFA-1, VLA-4. anti-LFA-1β plus VLA-4α MoAbs or anti-ICAM-1 MoAb added to the monolayers resulted in a complete inhibition of adhesion to parenchymal monolayers. In contrast, the addition of anti-IL-7 or anti-lL-7R MoAbs were able to block the augmented adhesiveness of CD4+CD23+ cells to monolayers observed in the presence of IL-7. Conclusion Taken together these findings point to the likelihood that IL-7 is responsible for the observed quantitative difference in the level of adhesion molecules and may open a new role of CD23 in the immune regulation. [ABSTRACT FROM AUTHOR]

Background and Objective. The mechanisms operative in specific immunotherapy (SIT) of Type I allergy are not completely understood. In the present study we evaluated immunological changes during SIT in pollinosis. Method. Eight patients suffering from pollinosis (monosensitized to grass pollen) were treated with conventional SIT. All subjects had IgE specific for Ph1 p 1, a major allergen of timothy grass. In vitro changes in the immunological reactivity to grass pollen extract and to recombinant Ph1 p 1 were evaluated. Subjects were examined at three occasions: before, after 3 months and after 1 year of SIT. Results. Serological analysis revealed a marked increase of grass pollen- and Ph1 p 1-specific IgG, titres of specific IgE did not change significantly. Lymphoproliferative responses to grass pollen extract and rPh1 p 1 were reduced already after 3 months of treatment. Accordingly, the cloning efficiency for Ph1 p 1-specific T-cell clones (TCC) dropped markedly in all patients. The majority of allergen-specific TCC raised before SIT revealed a TH2-like pattern of cytokine production. TCC established after SIT revealed TH1 characteristics. This shift was due to a decrease in IL-4 rather than an increase of IFN-production by T cells. Investigations of the epitopes recognized by T cells before and after SIT did not reveal the outgrowth of new ('protecting') specificities. We could not observe induction of allergen-specific CD8+ lymphocytes (supressor cells). Conclusion Our data indicate that &mdash on the level of TH lymphocytes — SIT induces tolerance to the allergen and a modulation of the cytokine pattern produced in response to allergen stimulation. [ABSTRACT FROM AUTHOR]

Background Previous studies have suggested varying molecular weights for mast cell derived tumour necrosis factor alpha (TNFα) and little data exist upon the factors which may regulate the control of this cytokine in these cells. Objective To determine the molecular weight of canine mastocytoma-derived TNFα, to determine whether it is pre-formed within the granule and whether its expression could be up-regulated by stem cell factor (SCF). Methods Molecular sizing was assessed by immunoblot. The cellular localization of the TNFα was determined by immunocytochemistry before and after stimulation by A23187 and passive sensitization. Subcellular localization was performed by immunogold immunocytochemistry. Changes in the level of mastocytoma mRNA for TNFα in response to stimulation with SCF or fibroblast conditioned media for up to 12 weeks were studied using Northern analysis and changes in the level of TNFα protein expression on immunoblot and immunocytochemistry. Results Mast cells contained authentic 17 kDa TNFα as identified by immunoblotting. Immunocytochemical studies demonstrated preformed TNFα which was released by stimulation with antigen after passive sensitization, or by the calcium ionophore A23I87. Further confirmation of the preformed nature of this TNFα was provided by immunogold electron microscopy which localized this cytokine to the granule of the inactive mast cell. Northern blotting revealed a constitutive message for TNFα, which increased in response to fibroblast conditioned media (FCM) and to recombinant human SCF. Immunocytochemical studies of mast cells cultured long-term with FCM or with recombinant SCF showed increased expression of TNFα over the course of 12 weeks incubation with these stimuli. Conclusion Mastocytoma derived-TNFα is a preformed, granule-associated 17 kDa cytokine which is released on stimulation with A23187 or passive sensitization. It is up-regulated by stem cell factor and by FCM over the course of 12 weeks. [ABSTRACT FROM AUTHOR]

This article describes evidence for cell-mediated hypersensitivity as an important pathogenetic mechanism in food intolerance. The capacity of activated T cells to cause tissue damage is beyond dispute. Delayed hypersensitivity lesions mediated by CD4+ T cells are the cause of tissue damage in a host of diseases, classically in pulmonary tuberculosis and contact sensitivity and, by definition, cytotoxic T cells cause cellular destruction and tissue damage. The principal of this test, first developed in the 1960s, is that antigen-specific T cells release factors when restimulated in vitro. These factors then prevent the migration of monocytes or leucocytes.