Phenotypic characterization of T lymphocytes emigrating into lung tissue and the airway lumen after antigen inhalation in sensitized mice.

Kennedy, Jeffrey D.; Hatfield, Cheryl A.; Fidler, Stephen F.; Winterrowd, Greg E.; Haas, Joseph V.; Chin, Jia En; Richards, Ivan M.

doi:10.1165/ajrcmb.12.6.7766426

Cited by 65 publications

(42 citation statements)

References 50 publications

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“…Our CD4 ϩ :CD8 ϩ T cell ratio of 2.3:1 is similar to the 3:1 to 4:1 ratio observed by others in acute OVA challenged C57BL/6J mice. 11 These BAL profiles changed dramatically with chronic (6-week) OVA challenge, such that the lymphocyte profile was 11% B cells, 7% TCR␥␦ cells, 28% CD4 ϩ TCR␣␤ cells, and 46% CD8 ϩ TCR␣␤ cells. It should be noted that the total number of lymphocytes was 17-fold less in the chronic than acute animals, reflecting the lesser degree of airway inflammation in these mice.…”

Section: Discussionmentioning

confidence: 96%

Shifts in Lung Lymphocyte Profiles Correlate with the Sequential Development of Acute Allergic and Chronic Tolerant Stages in a Murine Asthma Model

Yiamouyiannis

Schramm

Puddington

et al. 1999

The American Journal of Pathology

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T lymphocytes have a central regulatory role in the pathogenesis of asthma. We delineated the participation of lymphocytes in the acute allergic and chronic tolerant stages of a murine model of asthma by characterizing the various subsets of lymphocytes in bronchoalveolar lavage and lung tissue associated with these responses. Acute (10-day) aerosol challenge of immunized C57BL/6J mice with ovalbumin resulted in airway eosinophilia , histological evidence of peribronchial and perivascular airway inflammation, clusters of B cells and TCR␥␦ cells in lung tissue, increased serum IgE levels , and airway hyperresponsiveness to methacholine. In mice subjected to chronic (6-week) aerosol challenge with ovalbumin, airway inflammation and serum IgE levels were significantly attenuated and airway hyperresponsiveness was absent. The marked increases in lung B and T cell populations seen in the acute stage were also significantly reduced in the chronic stage of this model. Thus , acute ovalbumin challenge resulted in airway sensitization characteristic of asthma, whereas chronic ovalbumin challenge elicited a suppressed or tolerant state. The transition from antigenic sensitization to tolerance was accompanied by shifts in lymphocyte profiles in the lung and bronchoalveolar lavage fluid. Asthma is the most common chronic illness in developed countries. Our current understanding of the pathophysiology of allergic asthma is that it occurs from a breakdown of the normal tolerance to inhaled antigens, as a result of complex interactions between host and environmental factors. Emerging evidence suggests that the development of clinical sensitivity versus normal tolerance to inhaled antigens involves the establishment of a dominant population of CD4 ϩ T lymphocytes that are either classified as Th2-like (sensitization) or Th1-like (tolerance).1 Th2 responses are characterized by secretion of the cytokines interleukin (IL)-4 and IL-13, which induce the production of IgE by B cells, 2-5 and IL-5, which regulates the growth, differentiation, and activation of eosinophils.6 Conversely, Th1 responses are characterized by secretion of IL-2, tumor necrosis factor (TNF)-␤, and interferon (IFN)-␥. IFN-␥ has been shown to stimulate low-level IgG production and to potently inhibit IL-4-mediated IgE responses both in vivo and in vitro.7 The mechanisms that control CD4 ϩ T lymphocyte polarization into either Th1 or Th2 phenotypes are incompletely understood but appear to involve genetic predispositions, local factors such as existing cytokine concentrations and inflammation, and antigenic factors such as the potency, dose, and duration of exposure of the eliciting antigen. In susceptible individuals, antigen sensitization results in specific local and systemic IgE production and airway eosinophilia, which in turn induce the airway inflammation, airway hyperresponsiveness, and reversible airway obstruction characteristic of asthma.The factors influencing antigen sensitization or tolerance can be better studied in mice, given their well defined...

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Section: Discussionmentioning

confidence: 96%

Shifts in Lung Lymphocyte Profiles Correlate with the Sequential Development of Acute Allergic and Chronic Tolerant Stages in a Murine Asthma Model

Yiamouyiannis

Schramm

Puddington

et al. 1999

The American Journal of Pathology

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“…5). CD4 ϩ T cells from animals initially exposed to 2 and 4 wk of OVA expressed not only similar levels of the early activation marker CD69 (34,35) and the IL-2R CD25 (36,37), but also similar levels of T1/ST2, a marker of Th2 differentiation and a necessary factor in the development of eosinophilic airway inflammation (38 -40). The level of expression of these molecules was substantially higher than previously documented in naive animals.…”

Section: Discussionmentioning

confidence: 99%

Chronic Exposure to Innocuous Antigen in Sensitized Mice Leads to Suppressed Airway Eosinophilia That Is Reversed by Granulocyte Macrophage Colony-Stimulating Factor

Świrski

Sajic

Robbins

et al. 2002

The Journal of Immunology

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In this study we investigated the impact of chronic allergen exposure on airway inflammation and humoral responses in sensitized mice. We observed marked eosinophilia in the bronchoalveolar lavage, lung tissue, and peripheral blood after 2 wk of exposure. In contrast, eosinophilia was markedly reduced by 3 wk and completely resolved by 4 wk of exposure, despite the continued presence of Ag. Decreases in airway eosinophilia were associated with a robust humoral response. We observed that levels of OVA-specific IgE, IgG1, and IgG2a increased during the course of exposure. To assess whether continuous exposure to Ag impacts the ability of the lung to respond to subsequent Ag challenge, mice were exposed to either 2 or 4 wk of OVA in the context of GM-CSF. All groups were then rested for 28 days and exposed to OVA on three consecutive days. We observed a significant decrease in airway eosinophilia and IL-5 expression in the bronchoalveolar lavage and serum in mice initially exposed to 4 wk of OVA, compared with animals exposed to 2 wk only. However, in both groups expression of B7.2 on dendritic cells as well as CD25, CD69, and T1/ST2 on CD4+ T cells was enhanced, suggesting immune activation. Delivery of rGM-CSF fully restored airway eosinophilia. This study shows that exposure to innocuous Ag alone does not lead to persistent eosinophilic airway inflammation, but rather to abrogated eosinophilia. This suppression can be reversed by GM-CSF.

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“…In ovalbumin-sensitized and challenged mice, 50-90% of lung tissue and BAL T-cells expressed ICAM-1, together with LFA-1 and VLA-4 [83]. Recently, we have found that by comparison with blood in which expression of ICAM-1 is low, a greater proportion of CD3+ T-cells in induced sputum express ICAM-1 in both normals and mild asthmatics [13].…”

Section: Icam-1 In Allergic Inflammation and Asthmamentioning

confidence: 96%

The role of ICAM-1 on T-cells in the pathogenesis of asthma

Stanciu¹,

Djukanović²

1998

Eur Respir J

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The capacity of inflammatory cells to adhere is critical to inflammatory responses and involves an array of adhesion molecules grouped into distinct families. Intercellular adhesion molecule (ICAM)-1 has recently attracted much interest in view of increasing evidence that it plays a prominent role in allergic diseases such as asthma and rhinitis. Apart from its role in adhesion of inflammatory cells to vascular endothelium, the extracellular matrix and epithelium, ICAM-1 mediates T-cell/T-cell, T-cell/target cell and T-cell/B-cell interactions. ICAM-1 on the surface of T-cells is thought to participate in signal transduction and may thus modulate several functions including activation, proliferation, cytotoxicity and cytokine production. Because ICAM-1 is the receptor for the major group of rhinoviruses, the most important cause of acute asthma attacks, binding of rhinovirus (RV) to ICAM-1 on T-cells may, at least theoretically, modulate their function. We review here the role of ICAM-1 in asthma and focus more specifically on its expression on T-cells. We present evidence for a general increase in ICAM-1 expression in this disease including recent observations of enhanced expression on the surface of T-cells in the airways lumen. Whilst the implications of intercellular adhesion molecule- upregulation in asthma remain to be fully elucidated, its participation in cell trafficking and activation are being considered as a target for treatment. We present here early attempts to interfere with intercellular adhesion molecule-1 as an adhesion molecule involved in cell influx and studies aimed preventing virus-induced exacerbations of asthma in children based on the knowledge that intercellular adhesion molecule-1 is the receptor for rhinoviruses.

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Phenotypic characterization of T lymphocytes emigrating into lung tissue and the airway lumen after antigen inhalation in sensitized mice.

Cited by 65 publications

References 50 publications

Shifts in Lung Lymphocyte Profiles Correlate with the Sequential Development of Acute Allergic and Chronic Tolerant Stages in a Murine Asthma Model

Shifts in Lung Lymphocyte Profiles Correlate with the Sequential Development of Acute Allergic and Chronic Tolerant Stages in a Murine Asthma Model

Chronic Exposure to Innocuous Antigen in Sensitized Mice Leads to Suppressed Airway Eosinophilia That Is Reversed by Granulocyte Macrophage Colony-Stimulating Factor

The role of ICAM-1 on T-cells in the pathogenesis of asthma

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