Bronchial CD8 Cell Infiltrate and Lung Function Decline in Asthma

Rensen, Elizabeth L J van; Sont, Jacob K.; Evertse, Christine E.; Willems, L. N. A.; Mauad, Thaís; Hiemstra, Pieter S.; Sterk, Peter J.

doi:10.1164/rccm.200504-619oc

Cited by 132 publications

(92 citation statements)

References 33 publications

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“…In asthma patients, airway infiltrating CD8 ϩ T cells have the capacity to produce Th2 cytokines and modulate the disease (21), increased numbers of CD8 ϩ T cells in the airways have been found in the lungs of patients after a fatal asthma attack (40), and the number of bronchial wall CD8 ϩ T cells but not the number of eosinophils or thickness of the basement membrane correlated with decline in lung function (41). Based on these data, CD8…”

Section: Discussionmentioning

confidence: 99%

CD8+ T Cell-Mediated Airway Hyperresponsiveness and Inflammation Is Dependent on CD4+IL-4+ T Cells

Koya

Miyahara

Takeda

et al. 2007

The Journal of Immunology

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CD4+ T cells, particularly Th2 cells, play a pivotal role in allergic airway inflammation. However, the requirements for interactions between CD4+ and CD8+ T cells in airway allergic inflammation have not been delineated. Sensitized and challenged OT-1 mice in which CD8+ T cells expressing the transgene for the OVA257–264 peptide (SIINFEKL) failed to develop airway hyperresponsiveness (AHR), airway eosinophilia, Th2 cytokine elevation, or goblet cell metaplasia. OT-1 mice that received naive CD4+IL-4+ T cells but not CD4+IL-4− T cells before sensitization developed all of these responses to the same degree as wild-type mice. Moreover, recipients of CD4+IL-4+ T cells developed significant increases in the number of CD8+IL-13+ T cells in the lung, whereas sensitized OT-1 mice that received primed CD4+ T cells just before challenge failed to develop these responses. Sensitized CD8-deficient mice that received CD8+ T cells from OT-1 mice that received naive CD4+ T cells before sensitization increased AHR and eosinophil numbers in bronchoalveolar lavage fluid when challenged with allergen. In contrast, sensitized CD8-deficient mice receiving CD8+ T cells from OT-1 mice without CD4+ T cells developed reduced AHR and eosinophil numbers in bronchoalveolar lavage fluid when challenged. These data suggest that interactions between CD4+ and CD8+ T cells, in part through IL-4 during the sensitization phase, are essential to the development of CD8+IL-13+ T cell-dependent AHR and airway allergic inflammation.

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Section: Discussionmentioning

confidence: 99%

CD8+ T Cell-Mediated Airway Hyperresponsiveness and Inflammation Is Dependent on CD4+IL-4+ T Cells

Koya

Miyahara

Takeda

et al. 2007

The Journal of Immunology

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“…In human asthma, BAL LTB4 levels have also correlated with disease severity (51) and the number of bronchial CD8 T cells has correlated with decline in lung function (52). In preliminary studies of BAL from asthmatics but not nonasthmatics, CD8…”

Section: Discussionmentioning

confidence: 99%

The Leukotriene B4 Receptor (BLT1) Is Required for Effector CD8+ T Cell-Mediated, Mast Cell-Dependent Airway Hyperresponsiveness

Taube

Miyahara

Ott

et al. 2006

The Journal of Immunology

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Studies in both humans and rodents have suggested that CD8+ T cells contribute to the development of airway hyperresponsiveness (AHR) and that leukotriene B4 (LTB4) is involved in the chemotaxis of effector CD8+ T cells (TEFF) to the lung by virtue of their expression of BLT1, the receptor for LTB4. In the present study, we used a mast cell-CD8-dependent model of AHR to further define the role of BLT1 in CD8+ T cell-mediated AHR. C57BL/6+/+ and CD8-deficient (CD8−/−) mice were passively sensitized with anti-OVA IgE and exposed to OVA via the airways. Following passive sensitization and allergen exposure, C57BL/6+/+ mice developed altered airway function, whereas passively sensitized and allergen-exposed CD8−/− mice failed to do so. CD8−/− mice reconstituted with CD8+ TEFF developed AHR in response to challenge. In contrast, CD8−/− mice reconstituted with BLT1-deficient effector CD8+ T cells did not develop AHR. The induction of increased airway responsiveness following transfer of CD8+ TEFF or in wild-type mice could be blocked by administration of an LTB4 receptor antagonist confirming the role of BLT1 in CD8+ T cell-mediated AHR. Together, these data define the important role for mast cells and the LTB4-BLT1 pathway in the development of CD8+ T cell-mediated allergic responses in the lung.

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“…It is tempting to speculate that fractalkine, which appears to be increased within epithelial and subepithelial areas of the airways in our severe PAH patients, could trigger smooth muscle hypertrophy [7] around the airways that could account for peripheral airway obstruction and hyperresponsiveness. Airway infiltration by CD8+ T-cells has been observed in chronic obstructive pulmonary disease (COPD) c EUROPEAN RESPIRATORY JOURNAL VOLUME 34 NUMBER 6 [8], as well as in severe asthma [9] and has been related to lung function decline.…”

Section: To the Editorsmentioning

confidence: 99%

Small airway obstruction in severe pulmonary arterial hypertension correlates with increased airway CD8+ T-cells and fractalkine expression

Ars¹,

Thurion²,

Delos³

et al. 2009

Eur Respir J

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Bronchial CD8 Cell Infiltrate and Lung Function Decline in Asthma

Abstract: The outcome of asthma, as determined by the annual decline in FEV1, can be predicted by the bronchial CD8+ cell infiltrate. This suggests that the inflammatory phenotype in asthma has prognostic relevance, which may require phenotype-specific therapeutic strategies.

Cited by 132 publications

References 33 publications

CD8+ T Cell-Mediated Airway Hyperresponsiveness and Inflammation Is Dependent on CD4+IL-4+ T Cells

CD8+ T Cell-Mediated Airway Hyperresponsiveness and Inflammation Is Dependent on CD4+IL-4+ T Cells

The Leukotriene B4 Receptor (BLT1) Is Required for Effector CD8+ T Cell-Mediated, Mast Cell-Dependent Airway Hyperresponsiveness

Small airway obstruction in severe pulmonary arterial hypertension correlates with increased airway CD8+ T-cells and fractalkine expression

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