TCR usage and cytokine expression in peripheral blood and BAL T cells

Bakakos, Petros; Pickard, C.; Smith, Joan K.; Frew, Anthony J.

doi:10.1046/j.1365-2249.2002.01847.x

Cited by 7 publications

(3 citation statements)

References 37 publications

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“…Interestingly, ROBINSON et al [29] reported activation of CD4+ T cells in humans with allergic asthma and postulated that cytokines produced by activated Th2-type CD4+ T-cells may contribute to LAR. Th1 and Th2 responses, including cytokine-and chemokine-mediated responses, are well documented in allergic asthma [30][31][32]. Our observations indicate that activation state might be more critical than absolute numbers of T-cell subpopulations in establishing chronic disease.…”

Section: Discussionmentioning

confidence: 68%

Modelling asthma in macaques: longitudinal changes in cellular and molecular markers

Ayanoglu¹,

Desai²,

Fick³

et al. 2010

European Respiratory Journal

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The aim of the present study was to determine whether systemic sensitisation and chronic aeroallergen challenge in macaques replicate the classical and emerging immunology and molecular pathology of human asthma.Macaques were immunised and periodically challenged over 2 yrs with house dust mite allergen. At key time-points, serum, bronchoalveolar lavage (BAL) and bronchial biopsies were assayed for genes, proteins and lymphocyte subpopulations relevant to clinical asthma.Immunisation and periodic airway challenge induced changes in immunoglobulin E, airway physiology and eosinophilia consistent with chronic, dual-phase asthma. Sensitisation increased interleukin (IL)-1b and -6 concentrations in serum, and IL-13 expression in BAL cells. Airway challenge increased: early expression of IL-5, -6, -13 and -19, and eotaxin; and variable late-phase expression of IL-4, -5 and -13, and thymus-and activation-regulated chemokine in BAL cells. CD4+ lymphocytes comprised 30% of the CD3+ cells in BAL, increasing to 50% in the late phase. Natural killer T-cells represented ,3% of the CD3+ cells. Corticosteroid treatment reduced serum histamine levels, percentage of CD4+ cells and monocyte-derived chemokine expression, while increasing CD3+ and CD8+ cells in BAL.Sensitisation and periodic aeroallergen challenge of cynomolgus macaques results in physiological, cellular, molecular and protein phenotypes, and therapeutic responses observed in human asthma, providing a model system useful in target and biomarker discovery, and translational asthma research.KEYWORDS: Asthma, corticosteroid treatment, natural killer T-cell, primate model A sthma continues to present a significant unmet medical need [1] and the search for effective asthma drugs with novel mechanisms of action continues. Nonhuman primate models most closely replicate the genetics, physiology, immunology and pathology of the human disease [2][3][4]. The availability of these models uniquely allows examination of both induction of chronic allergy-driven airway inflammation and bronchoconstriction in a controlled setting, as well as identification of key mediators for the maintenance of chronic asthma. Additionally, these models provide a platform to assess pre-clinical safety, and proof of activity and efficacy for novel asthma therapeutics, under conditions that are observed in human patients.Models of asthma have been developed in a variety of common laboratory animals, including guinea pigs, rabbits, rats, mice, sheep, cats, dogs and macaques (see review by BICE et al.[5]).However, there are significant differences in airway architecture and immune responses to chronic allergen between species. Few species develop spontaneous allergic sensitivity to allergens, chronic or prolonged immune and inflammatory responses following pulmonary allergen exposure, progressive worsening of airway responses with repeated antigen challenge, and significant accumulation of lymphoid cells outside the bronchial-associated lymphoid tissue. Murine models have been instrumental ...

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Section: Discussionmentioning

confidence: 68%

Modelling asthma in macaques: longitudinal changes in cellular and molecular markers

Ayanoglu¹,

Desai²,

Fick³

et al. 2010

European Respiratory Journal

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“…These analyses demonstrated that the immune reaction in sarcoidosis was strongly compartmentalized and that interstitium and alveolar region differ in the composition of the T cell subpopulation (13). However, bronchoalveolar T cells may only reflect a small part of the lung T cell pool (13)(14)(15)(20)(21)(22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Interstitial Lung and Peripheral Blood T Cell Receptor Repertoire in Cigarette Smokers

Korn¹,

Wiewrodt²,

Walz³

et al. 2005

Am J Respir Cell Mol Biol

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T lymphocytes modulate the pulmonary inflammatory response. The aim of this study was to evaluate the clonality within the interstitial lung and peripheral blood T cell receptor (TCR) repertoire in smokers. Interstitial T lymphocytes were isolated from surplus tissue of 16 patients (63 +/- 9 [+/- SD] yr old, 11 male) undergoing surgery due to lung cancer (n = 15) or emphysema. TCR clonality was assessed by PCR amplification followed by spectratyping. Nearly all TCR of interstitial lung lymphocytes showed oligoclonal bands (CD4(+) subset 13/16 patients, 81%; CD8(+) 100%) indicating a specific differentiation. Peripheral blood T lymphocytes (PBL) TCR (especially CD4(+)) had less oligoclonal bands (CD4(+) 31%, CD8(+) 88%). Likewise, more oligoclonal bands were seen in lung TCR (total of 168 bands; 37 CD4(+); 131 CD8(+)), compared with 59 bands in PBL TCR (13 CD4(+); 46 CD8(+)). Intraindividual comparison revealed a more prominent difference in TCR oligoclonality between lung and blood in CD8(+) T cells (median of difference lung minus blood 5; interquartile range 1-10; P = 0.002) compared with CD4(+) T cells (median 2, 0-3, P = 0.039). Thus, TCR oligoclonality is preferentially found in the CD8(+) T cell subset, most distinctive in the lung. These findings indicate a specific interstitial T cell differentiation in response to local stimuli.

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“… 20 Similarly, another study demonstrated that the percentage of total CD3+ T cells in peripheral blood was similar in asthmatic patients and healthy control subjects. 21 …”

Section: Discussionmentioning

confidence: 99%

The profile of leucocytes, CD3+, CD4+, and CD8+ T cells, and cytokine concentrations in peripheral blood of children with acute asthma exacerbation

2017

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ObjectiveTo determine the leucocyte profile and cytokine concentrations in the peripheral blood of children with an acute asthma exacerbation (AAE).MethodsThis descriptive, cross-sectional study enrolled paediatric patients admitted to hospital for AAE. The severity of AAE was assessed using the paediatric asthma score (PAS). Peripheral blood samples were collected for automatic quantification of white blood cell counts, CD3+, CD4+, and CD8+ T cells populations by flow cytometry and cytokine concentrations by flow cytometry-assisted immunoassay.ResultsA total of 127 children with AAE and 30 healthy control subjects were included in the study. The proportion of paediatric patients with decreased CD3+, CD4+ and CD8+ T cells was significantly higher in those with severe AAE compared with those with mild-to-moderate AAE. The concentrations of interleukin (IL)-2, IL-8, IL-12, and IL-4 in paediatric patients with rhinovirus infection were significantly higher than in those without rhinovirus infection. IL-2, IL-4, IL-6, TNF-α and GM-CSF concentrations during AAE were significantly lower than control. IL-5 and IL-13 concentrations during AAE were significantly higher than control.ConclusionsThe decrease of CD3+, CD4+, CD8+ T cells and IL-2, IL-4, IL-6, TNF-α, and GM-CSF combined with the increase of IL-5 and IL-13, were associated with AAE in children with asthma.

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TCR usage and cytokine expression in peripheral blood and BAL T cells

Cited by 7 publications

References 37 publications

Modelling asthma in macaques: longitudinal changes in cellular and molecular markers

Modelling asthma in macaques: longitudinal changes in cellular and molecular markers

Characterization of the Interstitial Lung and Peripheral Blood T Cell Receptor Repertoire in Cigarette Smokers

The profile of leucocytes, CD3+, CD4+, and CD8+ T cells, and cytokine concentrations in peripheral blood of children with acute asthma exacerbation

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