Increases in Activated T Lymphocytes, Eosinophils, and Cytokine mRNA Expression for Interleukin-5 and Granulocyte/Macrophage Colony-stimulating Factor in Bronchial Biopsies after Allergen Inhalation Challenge in Atopic Asthmatics

Bentley, Andrew; Meng, Qiu; Robinson, David S.; Hamid, Qutayba; Kay, A. B.; Durham, S.R.

doi:10.1165/ajrcmb/8.1.35

Cited by 309 publications

(162 citation statements)

References 48 publications

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“…In cases of fatal asthma, the numbers of eosinophils were more closely related to the number of lymphocytes than in the nonfatal asthma and control cases. Numerous studies [3,12,15,16,19,20,24,[32][33][34] have shown increased numbers both of lymphocytes and eosinophils in asthmatic airways, although not over the range of asthma severity and airway sizes sampled in this study. It has been suggested that cell/ endothelial adhesion mechanisms and chemoattractant cytokines [35][36][37][38] may provide a common pathway of extravasation for lymphocytes and eosinophils at sites of inflammation.…”

Section: Discussionmentioning

confidence: 52%

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The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics

Carroll

Cooke²,

James³

1997

Eur Respir J

248

163

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Airway inflammation in asthma consists of variably increased numbers of mononuclear and polymorphonuclear cells, and there is a growing body of evidence to suggest a primary role for lymphocytes and eosinophils in the pathogenesis of asthma. The aim of this study was to examine the distribution of lymphocytes and eosinophils in the bronchial tree of cases of mild and severe asthma.In cases of fatal asthma (n=10), nonfatal asthma (sudden nonrespiratory death with a history of asthma n=10), and control cases (sudden death with no history of respiratory illness, n=10), lymphocytes and eosinophils were counted in transverse sections of large and small airways stained with haematoxylin and eosin.Cases of fatal asthma had longstanding severe asthma and nonfatal cases generally had mild asthma. Lymphocytes were increased in all airway size groups both in fatal and nonfatal cases of asthma compared to control cases (p<0.001). Eosinophils were increased (p<0.001) in all airway size groups in the cases of fatal asthma compared to the nonfatal asthma and control groups, which were similar. These differences between case groups were of similar magnitude, when only a random single airway section from each case in each size group was examined. The numbers of lymphocytes correlated with the number of eosinophils in the fatal asthma group (r=0.60; p<0.0001), and to a lesser extent in the nonfatal (r=0.34; p=0.001) and control groups (r=0.32; p=0.001).These findings suggest that increased numbers of lymphocytes are uniformly distributed in the large and small airways in cases of asthma, independently of asthma severity, and that eosinophil recruitment may be related to asthma severity. Hence, biopsy specimens of the proximal airways are likely to be representative of the cellular infiltrate in large and small airways in mild and severe asthma.

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Section: Discussionmentioning

confidence: 52%

“…Immunohistochemical techniques have identified the CD4+ subset of T-lymphocytes in the airways of patients with asthma, and have demonstrated that these lymphocytes and eosinophils express markers of functional activation to a greater extent than those from nonasthmatic subjects [11,12,15,16].…”

mentioning

confidence: 99%

The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics

Carroll

Cooke²,

James³

1997

Eur Respir J

248

163

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“…1,2 Bronchoalveolar lavage (BAL) T cells from human asthmatics have been reported to express elevated levels of IL-4 and IL-5 mRNA. 3,4 In addition, an inverse association between Th1 tuberculin responses and asthma has been observed. 5,6 Current treatments for asthma are not satisfactory, and disease prevention is not possible.…”

Section: Introductionmentioning

confidence: 99%

A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma

et al. 2003

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Interleukin 4 (IL-4) is essential for the switching of B cells to IgE antibody production and for the maturation of T helper (Th) cells toward the Th2 phenotype. These mechanisms are thought to play a crucial role in the pathogenesis of the allergic airway inflammation observed in asthma. In the present study, we examined the anti-inflammatory effects of DNA administration of murine IL-4 mutant Q116D/Y119D (IL-4 double mutant, IL-4DM), which binds to the IL-4 receptor a and is an antagonist for IL-4. Immunization of BALB/c mice with alum-adsorbed ovalbumin (OVA) followed by aspiration with aerosolized OVA resulted in the development of allergic airway inflammation. A single administration of IL-4DM DNA before the aerosolized OVA challenge protected the mice from the subsequent induction of allergic airway inflammation. Serum IgE level and extent of eosinophil infiltration in bronchoalveolar lavage (BAL) from IL-4DM DNA-administered mice were significantly lower than those in BAL from control plasmid-immunized mice. In our study, IL-4 or IL-4 mutants were not detected in sera from mice that had received a single administration of IL-4DM DNA. The results of this study provide evidence for the potential utility of IL-4 mutant antagonist DNA inoculation as an approach to gene therapy for asthma.

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“…T cells have an important role in sensitization and immune responses. They release IL-3, -4, and -5 and GM-CSF, a pattern compatible with predominant activation of the Th2-type cell population (5), suggesting that activated T cells may contribute to cause inflammation with eosinophil accumulation during allergen-induced asthma (6). Similar pathologic changes in the bronchus were also observed in nonatopic asthma (7).…”

mentioning

confidence: 67%

“…It is known that lymphocytes, especially Th2-type lymphocytes, infiltrate into the airway tissue in asthmatics (5,6). However, the mechanism of infiltration is not well-known.…”

Section: Discussionmentioning

confidence: 99%

T Cells of Atopic Asthmatics Preferentially Infiltrate Into Human Bronchial Xenografts in SCID Mice

Tsumori

Kohrogi

Goto

et al. 2003

The Journal of Immunology

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T cells play an important role in the pathogenesis of bronchial asthma. However, it is not completely known how circulating lymphocytes infiltrate into the airways of asthmatic patients. Because SCID mice are unable to reject xenogenic transplants, many xenotransplant models using various human tissues have been developed. Therefore, to examine the interaction between bronchi and T lymphocytes of asthma, it may be possible to use the human bronchial xenograft and PBMC xenograft in SCID mice. We transplanted human bronchi into the subcutaneum of SCID mice and i.p. injected PBMCs that were obtained from patients with atopic asthma, atopic dermatitis and rheumatoid arthritis, and normal subjects (asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice). There was no difference in the percentage of CD3-, CD4-, CD8-, CD25-, CD45RO-, CD103-, and cutaneous lymphocyte Ag-positive cells in PBMCs among the patients with asthma, dermatitis, rheumatoid arthritis, and normal subjects, and CD3-positive cells in peripheral blood of asthmatic, dermatitis, rheumatic, and normal huPBMC-SCID mice. The number of CD3-, CD4-, and CD8-positive cells in the xenografts of asthmatic huPBMC-SCID mice was higher than those of dermatitis, rheumatic, and normal huPBMC-SCID mice. IL-4 mRNA and IL-5 mRNA were significantly higher in the xenografts of asthmatic huPBMC-SCID mice than those in the xenografts of normal huPBMC-SCID mice, but there were no significant differences in the expressions of IL-2 mRNA or IFN-γ mRNA between them. These findings suggest that T cells, especially Th2-type T cells, of asthmatics preferentially infiltrate into the human bronchi.

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Increases in Activated T Lymphocytes, Eosinophils, and Cytokine mRNA Expression for Interleukin-5 and Granulocyte/Macrophage Colony-stimulating Factor in Bronchial Biopsies after Allergen Inhalation Challenge in Atopic Asthmatics

Cited by 309 publications

References 48 publications

The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics

The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics

A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma

T Cells of Atopic Asthmatics Preferentially Infiltrate Into Human Bronchial Xenografts in SCID Mice

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