The role of T lymphocytes in the pathogenesis of asthma

Larché, Mark; Robinson, Douglas S.; Kay, A. B.

doi:10.1067/mai.2003.169

Cited by 509 publications

(424 citation statements)

References 144 publications

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“…IL-5, one product of Th2 cells, has been shown to provide an essential signal for the expansion and mobilization of eosinophils from the bone marrow into the lung after allergen exposure. [1][2][3][4] In our experiments, IL-5 and IL-13 levels and the number of lymphocytes in the BALF were lower in mice receiving Ad-FasL than in control mice ( Figure 4, 6c and d). Eotaxin has been found to be the most potent chemokine for the recruitment of CD95 ligand and airway inflammation Y-H Chuang et al eosinophils.…”

Section: Discussionmentioning

confidence: 45%

“…AHR plays an important role in the pathogenesis of bronchial asthma. [1][2][3][4] The severity of this hyper-reactivity has been correlated with the number of Th2 cytokine-producing T cells and various inflammatory cells, predominantly eosinophils, in the airway. [1][2][3][4] Fas/FasL-mediated apoptosis is an important mechanism in the downregulation of T-cellmediated immune responses and resolution of inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] The severity of this hyper-reactivity has been correlated with the number of Th2 cytokine-producing T cells and various inflammatory cells, predominantly eosinophils, in the airway. [1][2][3][4] Fas/FasL-mediated apoptosis is an important mechanism in the downregulation of T-cellmediated immune responses and resolution of inflammatory responses. [19][20][21][22]32 The gld mutant mice, which express a dysfunctional FasL protein, develop prominent infiltration of inflammatory cells in the airway.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Several Th2 cytokines, such as IL-5 and IL-13, have the potential to modulate airway inflammation and AHR. 3,4 IL-5 regulates eosinophil function, including development, activation, migration, and survival of eosinophils. 5 The eosinophil is thought to be a major effector cell in the pathogenesis of allergen-mediated AHR.…”

Section: Introductionmentioning

confidence: 99%

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Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Chuang¹,

Cl²,

et al. 2004

Gene Ther

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Allergic asthma is characterized by airway hyper-responsiveness (AHR) and cellular infiltration of the airway with predominantly eosinophils and Th2 cells. The normal resolution of inflammation in the lung occurs through the regulated removal of unneeded cells by Fas-Fas ligandmediated apoptosis. Fas ligand (FasL) is a member of the tumor necrosis factor family, and when bound to Fas, it induces apoptosis of the cells. To examine the effect of the FasL gene on airway inflammation and immune effector cells in allergic asthma, recombinant adenovirus expressing murine FasL (Ad-FasL) was delivered intratracheally into ovalbumin (OVA)-immunized mice. We found that a single administration of Ad-FasL in OVA-immunized mice significantly alleviated AHR and eosinophilia by inducing the apoptosis of eosinophils and/or reducing eosinophil attractant factors, such as IL-5 and eotaxin levels. The number of infiltrated lymphocytes and Th2 cytokines, including IL-5 and IL-13, decreased in OVA-immunized mice by administration of Ad-FasL. KC and TNF-a production also decreased in AdFasL-treated OVA-immunized mice. These findings indicated that the administration of Ad-FasL to OVA-sensitized mice significantly suppressed pulmonary allergic responses. Although more studies are needed, these results suggested that Ad-FasL might be applied as an alternative therapy for allergic asthma.

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Section: Discussionmentioning

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Chuang¹,

Cl²,

et al. 2004

Gene Ther

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“…1,2 Asthma has been recognized as one of the Th2-mediated diseases with a particular profile of cytokine responses. 3 It is, however, evident that other cytokines, classically considered as Th1-specific types, are also associated with the inflammatory responses that characterize chronic asthma. The prevalence of individuals with atopic diseases has increased in recent years, which has become one of the major concerns to the public health.…”

Section: Introductionmentioning

confidence: 99%

A promoter nucleotide variant of the dendritic cell-specific DCNP1 associates with serum IgE levels specific for dust mite allergens among the Korean asthmatics

Kim

et al. 2007

Genes Immun

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Dendritic cells (DCs), the most abundant antigen-presenting cells in the lung, have been drawing attention for their roles in specific allergic responses to aeroallergens with support of Th lymphocytes, and in persistent inflammatory changes in allergic asthma. To identify genetic factors that may be involved in the asthma susceptibility and development of the disease phenotypes, we examined association of DC-specific DCNP1 polymorphisms with the disease risk. The case-control study revealed association of the nucleotide variants with serum immunoglobulin E (IgE) levels specific for Dermatophagoides farinae (Der f 1) and Dermatophagoides pteronyssinus (Der p 1), major aeroallergens of dust mites, among subjects with asthma. In particular, the T-allele-carrying genotype frequencies for one of the variants (c.À1289C4T) located in the promoter region were found increased in the asthmatic group with low levels of the mite-specific IgE (odds ratio (OR) ¼ 0.63 (0.48-0.83) for Der p 1). Results from functional analyses indicated that the promoter variant would affect the gene expression by modulating DNA-protein interaction. We propose that the genetic polymorphism of DCNP1 may influence production of specific IgE by altering DC functions in the mite allergen presenting and/or processing. The functional relevance of the genetic variation would provide an important insight into the genetic basis of allergic response to the mite antigens.

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Allergic Asthma and Rhinitis: Toxicological Considerations

Regal¹

2009

General, Applied and Systems Toxicology

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Immunotoxicity can manifest as an exaggerated immune response to a normally innocuous substance and lead to hypersensitivity or allergic reactions in the lung. Allergens are encountered environmentally or in the workplace and can be low‐ and high‐molecular‐weight substances. Allergic asthma and allergic rhinitis are examples of allergic reactions in the lung with immediate, late and chronic phases contributing to respiratory tract pathology. Mechanistically, allergic asthma and rhinitis reflect a combination of antibody and cell‐mediated immune reactions involving IgE antibody to allergen in the early stages and Th2 cell involvement as the disease progresses to late‐phase reactions and chronic allergic inflammation. Multiple cell types and mediators are involved in the inflammatory response in the lung. Mechanistic differences leading to the asthma/rhinitis phenotype have been noted with different allergens, primarily low‐molecular‐weight substances. Xenobiotics that are not allergens themselves may enhance the immune response to allergens or exacerbate pre‐existing asthma and airway hyper‐responsiveness. The complexity of the allergic response in terms of humoral and cell‐mediated immunity, as well as potential differences in mechanisms depending on the allergen, present a very challenging scenario for the toxicologist to predict the exposures that will result in allergic rhinitis or asthma.

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The role of T lymphocytes in the pathogenesis of asthma

Cited by 509 publications

References 144 publications

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

A promoter nucleotide variant of the dendritic cell-specific DCNP1 associates with serum IgE levels specific for dust mite allergens among the Korean asthmatics

Allergic Asthma and Rhinitis: Toxicological Considerations

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