Allergic and Nonallergic Asthmatics Have Distinct Patterns of T-Cell Activation and Cytokine Production in Peripheral Blood and Bronchoalveolar Lavage

Walker, Christoph; Bode, Erhard; Boer, Liesbeth; Hansel, Trevor T.; Blaser, Kurt; Virchow, J. Christian

doi:10.1164/ajrccm/146.1.109

Cited by 734 publications

(454 citation statements)

References 10 publications

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“…The reports of increased IL-5 protein levels in the BAL fluid, serum and peripheral blood T cell supernatants of asthmatics (Walker et al 1992, Motojima et al 1993, support the findings of increased numbers of IL-5 mRNA positive cells in these biological fluids. In addition, T cell lines that have been established from the BAL fluid and peripheral blood of atopic asthmatics secrete increased levels of IL-5 compared to atopic and non-atopic controls, thus providing further evidence that T cells in asthma have a propensity to make both IL-5 mRNA transcripts and IL-5 translated product which can then activate eosinophils (Endo et al 1993, Okudaira et al 1995, Till et al 1995.…”

Section: Asthma and Il-5 Human Studies: Il5 Mrna And Proteinsupporting

confidence: 73%

“…In addition, the increased expression of IL-5 mRNA in BAL has been directly correlated to asthma symptom severity and inversely correlated to abnormal airway physiology ). Finally, in the studies where increased IL-5 protein levels were demonstrated in the BAL fluid, serum and peripheral blood T cell supernatants (Walker et al 1992, Motojima et al 1993 of asthmatic subjects, the IL-5 protein levels detected correlated with the numbers of eosinophils present in these fluids (Walker et al 1992).…”

Section: Asthma and Il-5 Human Studies: Il5 Mrna And Proteinmentioning

confidence: 90%

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IL-5 and IL-5 receptor in asthma

Kotsimbos

Hamid

1997

Mem. Inst. Oswaldo Cruz

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and a soluble isoform (αIL-5Rs). Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS). JAK2, STAT1 and STAT 5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities in FEV1, airway reactivity and clinical severity in asthma. It has now been well documented that IL-5 is highly expressed in the bronchial mucosa of atopic and intrinsic asthmatics and that the increased IL-5 mRNA present in airway tissues is predominantly T cell derived. Immunocytochemical staining of bronchial biopsy sections has confirmed that IL-5 mRNA transcripts are translated into protein in asthmatic subjects. Furthermore, the number of activated CD 4 + T cells and IL-5 mRNA positive cells are increased in asthmatic airways following antigen challenge and studies that have examined IL-5 expression in asthmatic subjects before and after steroids have shown significantly decreased expression following oral corticosteroid treatment in steroid-sensitive asthma but not in steroid resistant and chronic severe steroid dependent asthma. The link between T cell derived IL-5 and eosinophil activation in asthmatic airways is further strengthened by the demonstration that there is an increased number of αIL-5R mRNA positive cells in the bronchial biopsies of atopic and non-atopic asthmatic subjects and that the eosinophil is the predominant site of this increased

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Section: Asthma and Il-5 Human Studies: Il5 Mrna And Proteinsupporting

confidence: 73%

Section: Asthma and Il-5 Human Studies: Il5 Mrna And Proteinmentioning

confidence: 90%

IL-5 and IL-5 receptor in asthma

Kotsimbos

Hamid

1997

Mem. Inst. Oswaldo Cruz

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“…Previous studies have reported that BAL concentrations of IL-4 and IL-5 protein were similar in asthmatic and healthy subjects [27], while others have reported increased IL-4 and IL-5 protein concentrations in BAL fluid and in culture supernatants from PB and BAL T cells of allergic asthmatics as compared to normal subjects [3]. This is not necessarily inconsistent with our findings, but could reflect increased production of Th2 cytokines by small numbers of cells in each compartment, rather than an increased number of Th2-cytokine producing T cells.…”

Section: Discussionmentioning

confidence: 90%

“…T lymphocytes have been suggested to play an important role in regulating the inflammatory and immunological processes thought to underlie asthma [2], by manufacturing and releasing an array of cytokines and chemokines [2,3]. In particular, interferon-gamma (IFN-g) has many proinflammatory activities on endothelium and eosinophils [4,5], IL-4 and IL-13 promote isotype switching of B-lymphocytes towards IgE production and IL-5 is the main cytokine regulating the differentiation and activation of eosinophils [6,7].…”

Section: Introductionmentioning

confidence: 99%

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

Bakakos

Pickard

Smith

et al. 2002

Clinical and Experimental Immunology

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SUMMARY T cells are thought to play an important regulatory role in atopic asthma. We hypothesized that human blood and BAL T cell subsets bearing various TCR-Vβ genes might show selective differences in their cytokine profile. Peripheral blood (PB) and bronchoalveolar lavage (BAL) T cells from seven atopic asthmatic and six non-atopic non-asthmatic subjects were stimulated with PMA and ionomycin in the presence of monensin and analysed for TCR-Vβ expression and production of cytokines at the single cell level. The percentage of IFN-γ- and IL-2-producing BAL T cells was elevated compared with PB T cells from both the asthmatic subjects and the non-atopic, non-asthmatic controls. A small percentage of PB and BAL T cells produced IL-4 and IL-5, in asthmatic and normal subjects. In peripheral blood, the percentage of T cells expressing each cytokine was similar in the various TCR-Vβ subsets and in total CD3+ T cells in all normal and six of seven asthmatic subjects. However, there was a substantial degree of heterogeneity in the cytokine profile of BAL TCR-Vβ subsets compared with the total CD3+ T cells. This was more obvious in the asthmatic subjects with a reduction in the percentage of IFN-γ- and IL-2-expressing T cells (five of seven asthmatic subjects) and an increase in the percentage of IL-4- and IL-5-expressing T cells (two of seven asthmatic subjects). These data confirm previous findings of an elevated proportion of IFN-γ- and IL-2-producing BAL T cells while only a small proportion of PB and BAL T cells produce IL-4 and IL-5. Moreover, subsets of BAL T cells, defined by their TCR-Vβ usage, may differ in their cytokine profile compared with the total CD3+ T cells, implying that T cells expressing different Vβ elements may play different roles in regulating the airway inflammation in asthma.

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“…In experimented studies, in serum of mice exposed to diisocyanates by inhalation not only total IgE but also specific IgE, IgG and IL-2, 4, 5, and IFNγ were increased [58][59][60][61] . Inflammatory cell infiltrates in bronchial biopsies of patients suffering from isocyanate induced asthma include mast cells, eosinophils, and activated lymphocytes (bearing the IL-2 receptor (CD25)) 62,63) . The presence of activated lymphocytes and eosinophils in bronchial biopsies suggest that a T lymphocyte eosinophil interaction may be important in asthma of different origin, a hypothesis further supported by the finding of the cells expressing IL-5 messenger RNA in bronchial biopsies of asthmatics.…”

Section: Immunological Mechanisms and Clinical Responsesmentioning

confidence: 99%

Review of the occupational exposure to isocyanates: Mechanisms of action

Nakashima

Takeshita

Morimoto

2002

Environ Health Prev Med

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Polyurethanes are useful polymers in a large variety of technical and consumer products that are generally made from diisocyanates and polyols or similar compounds. Toluene diisocyanate (TDI), 4,4'-methylenediphenyl diisocyanate (MDI) and 1,6'-hexamethylene diisocyanate (HDI) are useful for polyurethane products. Isocyanates are reactive chemicals that can be handled without problems in manufacturing or technical environments. In general, consumers may only have contact with these chemicals on rare occasions. The objective of this study was to review the mechanisms of action of inhalation of isocyanates. This paper describes, in summary, the potential occupational exposure to isocyanates, the chemistry and reactivity of isocyanates, the results from genotoxicity studies, investigative toxicity studies, metabolism and results from epidemiology studies on isocyanate-exposed workers. The overall conclusion is that because humans are not exposed to high levels of respiratory isocyanate particles, concerns over the possible development of lung tumors should not be relevant. There are many mechanisms of action induced by isocyanates, but those entities are unclear. This is because these mechanisms act simultaneously and are complex.

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Allergic and Nonallergic Asthmatics Have Distinct Patterns of T-Cell Activation and Cytokine Production in Peripheral Blood and Bronchoalveolar Lavage

Cited by 734 publications

References 10 publications

IL-5 and IL-5 receptor in asthma

IL-5 and IL-5 receptor in asthma

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

Review of the occupational exposure to isocyanates: Mechanisms of action

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