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Natural Killer T Cells (natural + killer_t_cell)
Selected AbstractsNatural killer T cells are targets for human immunodeficiency virus infectionIMMUNOLOGY, Issue 1 2003Nadine Y. Crowe No abstract is available for this article. [source] Natural killer T cells expressing IFN-, and IL-4 in lesional skin of atopic eczemaALLERGY, Issue 11 2009D. Simon Background:, The inflammation of atopic eczema (AE) is orchestrated not only by T cells predominantly but also B cells, eosinophils and dendritic cells. Recently, a role of invariant natural killer T (NKT) cells has been reported in bronchial asthma and allergy. Natural killer T cells express a restricted repertoire of T-cell receptor ,/, and produce interferon (IFN)-, and/or interleukin (IL)-4 upon activation. Aim of the study:, To determine the presence of NKT cells in lesional AE skin in comparison with other eczematous disorders and to analyse their cytokine expression. Methods:, Immunofluorescence stainings were carried out using antibodies recognizing NKT cells, CD3+ and CD4+ cells, IFN-, and IL-4. Results:, Natural killer T cells have been detected in small numbers in the majority of AE specimens as well as in atopy patch test (APT) reactions, allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). In AE, the proportion of NKT cells among CD3+ cells was approximately 5%. NKT cells expressed both IFN-, and IL-4 in AE, APT and ACD but predominantly IFN-, in ICD. Conclusion:, Natural killer T cells are part of the inflammatory infiltrate of AE as well as APT, ACD and ICD, suggesting a pathogenic role of NKT cells in eczematous skin disorders. The pattern of IFN-, and IL-4 cytokine expression by NKT cells varied depending on the type of eczematous disease. [source] Natural killer T cells in families of patients with systemic lupus erythematosus: Their possible role in regulation of IGG productionARTHRITIS & RHEUMATISM, Issue 1 2007Matthew R. J. Green Objective To determine whether there is a link between the frequency of natural killer T (NKT) cells and high levels of IgG in patients with systemic lupus erythematosus (SLE) and their relatives. Methods Blood samples were obtained from patients with SLE, their first-degree relatives, patients with rheumatoid arthritis (RA), and healthy control subjects. The frequency of NKT cells (defined as CD56+ T cells) was expressed as a percentage of total blood lymphocytes. Plasma levels of total IgG and IgM, and IgG antibodies to double-stranded DNA (dsDNA) were determined. Results The frequency of NKT cells was lower in patients with SLE than in control subjects. No such decrease was observed in the relatives of patients with SLE or in patients with RA. High levels of IgG were observed in both patients with SLE and their relatives, while low levels of IgM were observed in these same groups. In relatives of patients with SLE, an inverse correlation between the frequency of NKT cells and IgG levels was observed. Moreover, raised levels of IgG in patients with SLE and their relatives and high levels of IgG anti-dsDNA in patients were associated with low frequencies of NKT cells. Conclusion These results suggest that NKT cells have an important role in the regulation of IgG production, although NKT cells with invariant T cell receptors may not necessarily be involved. NKT cells in the setting of SLE could lack the cytokine stimulus from NK or other cells that is needed to exert control on IgG production. Enhancement of NKT cell activity may provide a novel basis for therapy in SLE. [source] Natural killer T cells are dispensable in the development of allergen-induced airway hyperresponsiveness, inflammation and remodelling in a mouse model of chronic asthmaCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2010Y.-I. Koh Summary Natural killer T (NK T) cells have been shown to play an essential role in the development of allergen-induced airway hyperresponsiveness (AHR) and/or airway inflammation in mouse models of acute asthma. Recently, NK T cells have been reported to be required for the development of AHR in a virus induced chronic asthma model. We investigated whether NK T cells were required for the development of allergen-induced AHR, airway inflammation and airway remodelling in a mouse model of chronic asthma. CD1d,/, mice that lack NK T cells were used for the experiments. In the chronic model, AHR, eosinophilic inflammation, remodelling characteristics including mucus metaplasia, subepithelial fibrosis and increased mass of the airway smooth muscle, T helper type 2 (Th2) immune response and immunoglobulin (Ig)E production were equally increased in both CD1d,/, mice and wild-type mice. However, in the acute model, AHR, eosinophilic inflammation, Th2 immune response and IgE production were significantly decreased in the CD1d,/, mice compared to wild-type. CD1d-dependent NK T cells may not be required for the development of allergen-induced AHR, eosinophilic airway inflammation and airway remodelling in chronic asthma model, although they play a role in the development of AHR and eosinophilic inflammation in acute asthma model. [source] Clinical applications of natural killer T cell,based immunotherapy for cancerCANCER SCIENCE, Issue 4 2008Shinichiro Motohashi Human invariant V,24 natural killer T (NKT) cells are a novel, distinct lymphocyte population, characterized by an invariant T-cell receptor V,24 chain paired with V,11. V,24 NKT cells are activated by a specific glicolipid ligand, ,-GalCer, and rapidly produce a large amount of Th1 and Th2 cytokines, thereby modulating other immune cells such as antigen-specific CD4 and CD8 T cells, NK cells, and dendritic cells. Recent studies have shown that NKT cells play pivotal regulatory roles in many immune responses, including antitumor immunity. We herein review the quantitative alteration and functional deterioration of circulating V,24 NKT cells in various cancer-bearing patients. We also summarize the recent progress in the clinical studies of NKT cell-based tumor immunotherapy. Novel immunological results including the increased peripheral blood V,24 NKT cells and IFN-producing cells after the immunotherapy were revealed. The details of the safety profile and the antitumor responses were also disclosed. Although the objective clinical responses still remain unclear, some encouraging results have emerged. Therefore, NKT cell-based immunotherapy may potentially be an effective strategy for the treatment of cancer patients. (Cancer Sci 2008; 99: 638,645) [source] Phenotypic and genetic analyses of T-cell-mediated immunoregulation in patients with Type 1 diabetesDIABETIC MEDICINE, Issue 10 2006Y. Tsutsumi Abstract Aims To investigate the contribution of regulatory T cells and co-stimulatory molecules in CD4+ T cells to the development of Type 1 diabetes (T1D). Methods Twelve patients with T1D, nine patients with systemic lupus erythematosus (SLE), and 12 age-matched healthy control subjects participated. We analysed the proportions of CD25+CD4+ T cells and natural killer T cells (NKT cells), and the expression levels of Foxp3, CTLA-4, CD28, ICOS, PD-1 and BTLA in peripheral blood mononuclear cells and purified CD4+ T cells. Results There were no significant differences in the proportions of CD25+ CD4+ T cells or NKT cells among the three groups. PD-1 expression levels of peripheral CD4+ T cells from T1D patients were significantly lower than those from healthy control subjects (P = 0.00066). In contrast, PD-1 expression levels were similar in SLE patients and healthy control subjects. The expression levels of Foxp3, CTLA-4, CD28, ICOS and BTLA were similar in the three groups. Conclusions Decreased expression of the PD-1 gene in CD4+ T cells may contribute to the development and/or maintenance of autoimmune T1D. As the population studied was small and heterogeneous, further studies are required to confirm the findings. [source] CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2005Anja Marschner Abstract Human V,24+ V,11+ natural killer T cells (NKT cells) are "natural memory" T cells that detect glycolipid antigens such as ,-galactosylceramide (,-GalCer) presented on CD1d. In the present study we found that highly purified V,24+ NKT cells lack TLR9 mRNA, and thus are not sensitive towards stimulation with CpG oligodeoxynucleotides (ODN). Within PBMC, however, CpG ODN synergistically activated NKT cells stimulated with their cognate antigen ,-GalCer. Depletion of plasmacytoid dendritic cells (PDC) or myeloid dendritic cells (MDC) revealed that both DC subsets were necessary for the synergistic activation of NKT cells by ,-GalCer and CpG ODN. While PDC were responsible for the stimulation of NKT cells with CpG ODN, MDC but not PDC presented ,-GalCer via CD1d. Partial activation of NKT cells was mediated by PDC-derived IFN-,, whereas full activation of NKT cells as indicated by IFN,, production required cell-to-cell contact of PDC and NKT cells in addition to IFN-,; OX40 was involved in this interaction. We conclude that CpG-activated PDC enhance ,-GalCer-specific NKT cell activation, and bias activated NKT cells towards a Th1 phenotype. Our results lead to a novel concept of PDC function: to regulate effector activity of antigen-stimulated T cells in a cell contact-dependent manner without the need of simultaneous presentation of the cognate T cell antigen. [source] Activated CD1d-restricted natural killer T cells secrete IL-2: innate help for CD4+CD25+ regulatory T cells?EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2005Shuiping Jiang Abstract CD4+CD25+ and CD1d-restricted natural killer T (NKT) cells are thymus-derived self-reactive regulatory T,cells that play a key role in the control of pathological immune responses. Little is known about functional cooperation between innate regulatory NKT,cells and adaptive CD4+CD25+ regulatory cells. Here we show that human CD4+V,24+V,11+ (CD4+ NKT) cells isolated from peripheral blood by flow cytometric cell sorting secrete substantial amounts of IL-2 after stimulation with dendritic cells (DC) and ,-Galactosylceramide. When cocultured with CD4+CD25+ cells, CD4+ NKT,cells promoted moderate proliferation of CD4+CD25+ cells. The proliferation of CD4+CD25+ T,cells was due to soluble IL-2 produced by activated CD4+ NKT,cells. The expanded CD4+CD25+ cells remained anergic and retained their potent suppressive properties. These findings indicate that unlike conventional CD4+ and CD8+ T,cells, which are susceptible to CD4+CD25+ regulatory cell suppression, NKT,cells promote CD4+CD25+ regulatory cell proliferation. These data raise the possibility that NKT,cells can function as helper cells to CD4+CD25+ regulatory T,cells, thereby providing a link between the two naturally occurring populations of regulatory T,cells. [source] Neural cell adhesion molecule expression: No correlation with perineural invasion in cutaneous squamous cell carcinoma of the head and neckHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2009C. Arturo Solares MD Abstract Background. Perineural invasion (PNI) in cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is associated with decreased survival, particularly in patients with clinical signs of cranial nerve involvement. There is evidence to indicate that neural cell adhesion molecule (N-CAM) confers capability of PNI. We analyzed our own patient population to determine if N-CAM predicted clinical PNI in CSCCHN. Methods. Tissue from patients with CSCCHN and clinical PNI, who underwent surgery between 1998 and 2005, was immunostained for N-CAM. In addition, non-PNI CSCCHN and normal nerve sections were also stained. A section of neuroendocrine tumor was included in each slide as a positive control. In addition, most of the sections also had an "inbuilt control" in the CD56 positive natural killer T cells that formed part of the inflammatory reaction to the tumors. Results. Tissue was available from 14 patients with CSCCHN and clinical PNI. The analysis was carried out in 14 patients without PNI and 4 normal nerves. N-CAM was not expressed in any of our PNI CSCCHN specimens or non-PNI controls. It was strongly expressed in the neuroendocrine tumors and positive in-built controls, as well as in normal nerve tissue. Conclusion. N-CAM expression did not predict neurotropism in our patient population. Additional studies are required to identify the cell surface markers expressed by CSCCHN which confer neurotropism capabilities. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] Impact of class A, B and C CpG-oligodeoxynucleotides on in vitro activation of innate immune cells in human immunodeficiency virus-1 infected individualsIMMUNOLOGY, Issue 4 2007Jeffrey A. Martinson Summary Oligodeoxynucleotides (ODN) with unmethylated deoxycytidyl-deoxyguanosine dinucleotides (CpG-ODNs) stimulate Toll-like receptor 9 (TLR9) in plasmacytoid dendritic cells (pDC) and B cells and activate innate and adaptive immunity. Three classes of synthetic CpG-ODNs, class A, B and C, activate cells through TLR9; our goal was to evaluate their effect on cells from human immunodeficiency virus (HIV)-1+ individuals. We compared the frequencies and the unstimulated activation status of immune effector cells in HIV-1+ and HIV-1, individuals. Fewer pDC, myeloid dendritic cells (mDC), B cells, natural killer (NK) cells and invariant natural killer T cells (iNKT) were present in HIV-1+ peripheral blood mononuclear cells (PBMC) and their baseline activation status was higher than HIV-1, PBMC. Exposure of HIV-1+ PBMC to all classes of CpG-ODNs led to activation and maturation of pDC based on CD86, CD80, and CD83 expression similar to that of cells from HIV-1, individuals. The percentage of CpG-ODN stimulated pDC that express CD40 was dramatically higher when cells were obtained from HIV-1+ than from HIV-1, individuals. B-lymphocytes were activated similarly in HIV-1+ and HIV-1, individuals. mDC, NK and iNKT cell, which lack TLR9, were indirectly activated. Interferon-, (IFN-,) and interferon inducible protein 10 (IP-10) secretion was induced by class A or C but not class B CpG-ODN, but the concentrations were less than those produced by HIV-1, PBMC. HIV-1 infected individuals have fewer innate effector cells that are chronically activated, but these cells can be further activated by CpG-ODN, which suggests that synthetic CpG-ODNs could be used to enhance the immune system in HIV-1 infected individuals. [source] Age-dependent variation in the proportion and number of intestinal lymphocyte subsets, especially natural killer T cells, double-positive CD4+ CD8+ cells and B220+ T cells, in miceIMMUNOLOGY, Issue 3 2004Yuiko Ishimoto Summary The age-dependent variation in the proportion and number of lymphocyte subsets was examined at various extrathymic sites, including the liver, small intestine, colon and appendix in mice. In comparison with young mice (4 weeks of age), the number of total lymphocytes yielded by all tested organs was greater in adult (9 weeks) and old (40 weeks) mice. The major lymphocyte subset that expanded with age was interleukin-2 receptor (IL-2R) ,+ CD3int cells (50% of them expressed NK1.1) in the liver, whereas it was CD3+ IL-2R,, NK1.1, cells at all intraepithelial sites in the intestine. Although NK1.1+ CD3+ cells were present at intraepithelial sites in the intestine, the proportion of this subset was rather low. The ratio of CD4 to CD8 tended to decrease among natural killer T (NKT) cells and T cells at all intraepithelial sites in the intestine with age. A unique population of double-positive CD4+ CD8+ cells in the small intestine increased in old mice. B220+ T cells were found mainly in the appendix and colon, and the proportion of these T cells decreased in old mice. Conventional NKT cells were very few in J,281,/, and CD1d,/, mice in the liver, while NKT cells which existed in the appendix remained unchanged even in these mice. This was because unconventional CD8+ NKT cells were present in the intestine. The present results suggest that despite the fact that both the liver and intraepithelial sites in the intestine carry many extrathymic T cells, the distribution of lymphocyte subsets and their age-associated variation are site-specific. [source] CD1d-restricted natural killer T cells are potent targets for human immunodeficiency virus infectionIMMUNOLOGY, Issue 1 2003Richardson Fleuridor Summary Invariant human natural killer T cells (NKT) express a restricted T-cell receptor (TCR) V,24V,11 repertoire. These cells share both phenotypic and functional similarities between NK and T cells. Given the emerging role of NKT cells as critical cells in bridging the gap between innate and adaptive immunity, we examined their susceptibility to productive human immunodeficiency virus (HIV) infection by T-tropic, M-tropic, and primary isolates of HIV. We generated three human NKT cell clones (CA5, CA29, and CA31). Phenotypic characterization of these V,24+ V,11+ clones indicated that they were predominately positive for CD4, CD161, HLA-DR, CD38, CD45RO, and CD95 expression. The NKT cell clones expressed significantly more surface CCR5 molecules/cell and lower CXCR4 molecules/cell than phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PBMC). Consistent with the surface expression of CCR5 and CXCR4, the NKT clones were also selectively susceptible to HIV M-tropic, T-tropic, and primary isolate infection, as evaluated by both HIV p24 enzyme-linked immunosorbent assay and intracellular staining of HIV proteins. The amount of p24 production was dependent on the NKT clone studied and the HIV strain used. Clones CA29 and CA31 were also susceptible to HIV IIIB infection. The virions produced by these clones were able to productively infect PHA-stimulated PBMCs with the same kinetics as for primary infection of CD4+ blast. Collectively, this data demonstrates that NKT cells can be a target for productive HIV infection but with a lag in the time to peak p24 production. [source] Bacillus Calmette-Guérin-pulsed dendritic cells stimulate natural killer T cells and ,,T cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2007Michio Naoe Background: Immunotherapy with bacillus Calmette-Guérin (BCG) for bladder cancer is successful, although the precise mechanism is unclear. Natural killer (NK) cells are a candidate for BCG-activated killer cells, but the roles of other T lymphocytes, such as NKT cells and ,,T cells, are not fully understood. Mycobacterium tuberculosis is a potent activator of both NKT cells and ,,T cells. However, it is known that the patient's prognosis is good if there are increased numbers of dendritic cells (DCs) in the urine after BCG therapy. Therefore, we investigated whether DCs are matured by BCG and whether BCG-pulsed DCs stimulate NKT cells and ,,T cells. Methods: Naïve Pan T cells were isolated form peripheral blood mononuclear cells (PBMCs) and DCs were obtained by culturing CD14+ monocytes with granulocyte,macrophage colony-stimulating factor and interleukin-4. The DCs were pulsed with BCG and their maturation was measured by fluorescence-activated cell sorter analysis using the CD86 antibody. Naïve T lymphocytes were stimulated by coculture with BCG-pulsed DCs in vitro, followed by FACS analysis to estimate the ratio and activation of NKT cells and the ratio of ,,T cells. The 51Cr (chromium) release assay was used to estimate the cytotoxic activity of the stimulated T cells. Cytolytic proteins in the patient's PBMCs were measured during BCG therapy using semiquantitative reverse transcriptase-polymerase chain reaction. Results: The DCs were matured by BCG stimulation and the number of NKT cells and ,,T cells increased after culturing with BCG-pulsed DCs. The BCG-pulsed DCs also activated the NKT cells and ,,T cells. Also, the lymphocytes that were cocultured with the BCG-pulsed DCs showed unspecific cytotoxic activity against a bladder cancer cell line. Conclusion: Sensitization of NKT cells and ,,T cells by BCG-pulsed DCs might be one of the mechanisms of BCG immunotherapy. [source] Immunopathogenesis of psoriasis: focus on natural killer T cellsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2009S Peternel Abstract Psoriasis is a common inflammatory skin disease triggered by dysregulated immune response and characterized by hyperproliferation and altered differentiation of keratinocytes. Formation of psoriatic lesions is thought to be elicited by the complex cellular and cytokine network arising from the pathogenic interactions between keratinocytes and components of innate and acquired immune system. Natural killer T (NKT) cells are a heterogenous T-cell lineage that has been implicated in the pathogenesis of various autoimmune diseases including psoriasis. Due to the numerous functions of NKT cells that link innate and adaptive immunity, their role in psoriasis is complex and still elusive. We summarize the currently available literature data on this issue and discuss the possible role of NKT cells in the immunopathogenesis of this autoimmune disease. [source] Lactoferrin protects against concanavalin A-induced liver injury in miceLIVER INTERNATIONAL, Issue 4 2010Hao Yin Abstract Background: Liver diseases, caused by viral infection, autoimmune conditions, alcohol ingestion or the use of certain drugs, are a significant health issue, as many can develop into liver failure. Lactoferrin (Lac) is an iron-binding glycoprotein that belongs to the transferrin family. Owing to its multiple biological functions, Lac has been evaluated in a number of clinical trials to treat infections, inflammation and cancer. Aim: The present study aims to reveal a profound hepatoprotective effect of Lac, using a mouse model of Concanavalin A (Con A)-induced hepatitis, which mimics the pathophysiology of human viral and autoimmune hepatitis. Method: C57Bl/6J mice were injected with bovine Lac following Con A challenge. The effects of Lac on interferon (IFN)-, and interleukin (IL)-4 expression were determined. The roles of Lac on T-cell apoptosis and activation, and leukocytes infiltration were examined. Result: The data demonstrated that the protective effect of Lac was attributed to its ability to inhibit T-cell activation and production of IFN-,, as well as to suppress IL-4 production by hepatic natural killer T cells. Conclusion: These findings indicate a great therapeutic potential of Lac in treating in treating inflammatory hepatitis and possibly other inflammatory diseases. [source] Selective elimination of hepatic natural killer T cells with Concanavalin A improves liver regeneration in miceLIVER INTERNATIONAL, Issue 3 2006Wen Huang Abstract: Background: Although concanavalin A (Con A) as a T cell stimulant can cause natural killer T (NKT) cell-mediated liver injury in mice and a nonhepatotoxic dose of Con A can trigger innate immune cells including NKT cells to prevent tumor metastasis in the liver, little is known about the role of Con A-primed NKT cells in liver repair. In this study, we aimed to investigate the effect of pretreatment with a nontoxic dose of Con A on subsequent liver regeneration in mice. Methods: A nontoxic dose of Con A was injected intravenously 24 h before partial hepatectomy (PHx), which was used as a model of liver regeneration. Ratios of remnant liver mass to body weight, bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) labeling were used to assess liver regeneration. Results: Hepatic mononuclear cells were isolated and analyzed by flow cytometry. After PHx, the ratios of liver weight to body weight, PCNA-positive hepatocytes and BrdU-positive hepatocytes in Con A-pretreated mice were significantly higher than that of phosphate-buffered saline-treated mice, indicating that Con A pretreatment can accelerate liver regeneration. Flow cytometric analysis showed that NKT cells were significantly activated and selectively eliminated after the Con A administration. Moreover, NKT cells expressed more apoptosis-related molecules, Fas and Annexin V. Conclusions: Taken together, Con A accelerates liver regeneration in mice by eliminating hepatic NKT cells via activation-induced cell death. [source] Invariant natural killer T cells are natural regulators of murine spondylarthritisARTHRITIS & RHEUMATISM, Issue 4 2010Peggy Jacques Objective To investigate the role of invariant natural killer T (iNKT) cells in TNF,ARE/+ mice, an animal model of spondylarthritis (SpA) with both gut and joint inflammation. Methods The frequency and activation of iNKT cells were analyzed on mononuclear cells from the lymph nodes and livers of mice, using flow cytometry with ,-galactosylceramide/CD1d tetramers and quantitative polymerase chain reaction for the invariant V,14,J,18 rearrangement. Bone marrow,derived dendritic cells (DCs) were obtained by expansion of primary cells with granulocyte,macrophage colony-stimulating factor followed by coculture with iNKT cell hybridomas, and interleukin-2 release into the cocultures was then measured by enzyme-linked immunosorbent assay (ELISA). Cytokine levels were determined by ELISA or cytometric bead array analyses of freshly isolated DCs and iNKT cells in mixed cocultures. TNF,ARE/+ mice were backcrossed onto J,18,/, and CD1d,/, mice, and disease onset was evaluated by clinical scoring, positron emission tomography, and histology. CD1d levels were analyzed on mononuclear cells in paired blood and synovial fluid samples from patients with SpA compared with healthy control subjects. Results In the absence of iNKT cells, symptoms of gut and joint inflammation in TNF,ARE/+mice were aggravated. Invariant NKT cells were activated during the course of the disease. This was linked to an enrichment of inflammatory DCs, characterized by high levels of CD1d, particularly at draining sites of inflammation. A similar increase in CD1d levels was observed on DCs from patients with SpA. Inflammatory DCs from TNF,ARE/+ mice stimulated iNKT cells to produce immunomodulatory cytokines, in the absence of exogenous stimulation. Prolonged, continuous exposure, but not short-term exposure, to tumor necrosis factor (TNF) was found to be responsible for the enhanced DC,NKT cell crosstalk. Conclusion This mode of iNKT cell activation represents a natural counterregulatory mechanism for the dampening of TNF-driven inflammation. [source] Immunoglobulin E antibodies enhance pulmonary inflammation induced by inhalation of a chemical haptenCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2009C. B. Mathias Summary Background Occupational exposure to chemicals is an important cause of asthma. Recent studies indicate that IgE antibodies enhance sensitization to chemicals in the skin. Objective We investigated whether IgE might similarly promote the development of airway inflammation following inhalation of a contact sensitizer. Methods A model of chemical-induced asthma is described in which introduction of the low-molecular-weight compound, trinitrobenzene sulphonic acid (TNBS), via the respiratory tract was used for both sensitization and challenge. The role of IgE antibodies in the immune response to inhaled TNBS in this model was assessed by comparing the responses of wild-type (WT) and IgE-deficient (IgE,/,) mice on the BALB/c background. Reconstitution of circulating IgE levels by intravenous injection of IgE antibodies into IgE,/, mice before sensitization was performed to confirm the role of IgE in any differences observed between the responses of WT and IgE,/, mice. Results Intranasal challenge of TNBS-sensitized (but not sham-sensitized control mice) induced intense pulmonary inflammation. Macrophages, eosinophils and lymphocytes, including T, B, natural killer and natural killer T cells, were recruited to the airway and the animals displayed bronchial hyperresponsiveness (BHR) to methacholine. Serum levels of murine mast cell protease-1 (mMCP-1) were elevated suggesting mast cell activation. In contrast, the development of airway inflammation, recruitment of lymphocytes, induction of BHR and production of mMCP-1 were all significantly attenuated in IgE-deficient mice. Reconstitution of IgE,/, mice with IgE (of unrelated antigen specificity) before sensitization partially restored these features of asthma. Conclusion Our data indicate that IgE antibodies non-specifically enhance the development of airway inflammation induced by exposure to chemical antigens. [source] | ||||||||||||||||||||||