CD4 T-Lymphocyte Activation in Asthma Is Accompanied by Increased Serum Concentrations of Interleukin-5: Effect of Glucocorticoid Therapy

Abstract

Peripheral blood mononuclear cells (PBMC) and serum were obtained, on two occasions, from 15 asthmatic patients who required oral glucocorticoid therapy for moderate to severe disease exacerbations. Samples were obtained immediately before commencement of oral glucocorticoids (Day 1) and again after 7 days of treatment (Day 7), when lung function had significantly improved. Samples were also isolated on two occasions 7 days apart from a group of seven untreated volunteers. Expression of CD25, human lymphocyte antigen (HLA-)DR, CD45RA, and CD45RO on CD4 and CD8 T lymphocytes was measured by flow cytometry, and serum concentrations of interleukin-5 (IL-5) were measured using an enzyme-linked immunosorbent assay technique. On Day 1 the asthmatic patients showed significantly higher percentages, as compared with the control subjects of CD4 T lymphocytes expressing the markers CD25, HLA-DR, and CD45RO and significantly lower percentages of CD4 T cells expressing CD45RA. After glucocorticoid therapy, the percentages of CD4 T cells expressing CD25, HLA-DR, and CD45RO were significantly reduced in the asthmatic patients, and the percentages of those expressing CD45RA significantly increased so that by Day 7 expression of all four markers was no longer significantly different from that of the control subjects. By contrast, the percentages of CD8 T cells expressing HLA-DR, CD45RA, and CD45RO in the PBMC of the asthmatic patients on Day 1 were not significantly different from those in control subjects, whereas the percentages of CD25 expressing CD8 T cells were only marginally elevated. Glucocorticoid therapy resulted in no significant change in the expression of all four markers on CD T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of Activation Markers and Cytokine mRNA by Peripheral Blood CD4 and CD8 T Cells in Atopic and Nonatopic Childhood Asthma: Effect of Inhaled Glucocorticoid Therapy

“…These studies support a role for activated "Th2-type" T cells and their eosinophil-active cytokine products in the pathogenesis of child asthma and have reinforced observations in adult asthmatics that the properties of peripheral blood T cells, at least in terms of expression of activation markers and cytokine mRNA, closely resemble those of T cells in the bronchial mucosa and lumen. [5][6][7][8][9]13 One of our principal aims in the present study was to compare functional aspects of both CD4 and CD8 T cells in atopic and nonatopic child asthmatics. The rationale for this was based partly on our previous studies 15,16 demonstrating that CD8, as well as CD4 T cells, show evidence of activation in child atopic asthma, and on recent studies in adults 27 showing that both CD8 and CD4 T cells within the asthmatic bronchial mucosa are a source of mRNA encoding both IL-5 (the eosinophil-specific cytokine most strongly implicated in the regulation of asthma severity) and IL-4 (1 of only 2 cytokines shown to induce IgE synthesis in B cells and therefore implicated in the pathogenesis of atopy).…”

“…Previous evidence suggests that they do this at least partly by reducing T-cell activation and concomitant cytokine production. 7,13,14 The relative lack of knowledge about the molecular immunopathology of asthma in children stems partly from the practical and ethical problems with obtaining access to the bronchial mucosa. Fortunately, the studies on the properties of peripheral blood T cells in adult asthma cited above suggest that the properties of these cells reflect those of cells in the bronchial mucosa, owing perhaps to a "spillover" or recirculation of these cells into the peripheral circulation.…”

IL-5 Up-Regulates Cysteinyl Leukotriene 1 Receptor Expression in HL-60 Cells Differentiated into Eosinophils

“…Anti-inflammatory glucocorticoid therapy reduces IL-5 expression and suppresses airway eosinophilia in asthma (34,52). Thus, priming of eosinophils with cytokines such as IL-5 and the increase in cysLTs production in the airways of asthmatics may contribute to eosinophil influx and activation.…”

“…Moreover, treatment of normal eosinophils with IL-5, IL-3, or GM-CSF enhanced their cysLT production in vitro (28 -30). IL-5 is also synthesized by Th2 lymphocytes and mast cells in the asthmatic airway (31)(32)(33) and is detectable in the plasma of symptomatic asthmatics (34). The importance of IL-5 in pathogenesis is underscored by the findings that an anti-IL-5 Ab completely blocks eosinophilic airway infiltration in a mouse model of asthma (35).…”

The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness

“…Human asthma is associated with the presence of lung and peripheral eosinophilia and peribronchial infiltration of CD4 ϩ T cells producing type 2 cytokines, in particular IL-4, IL-5, and IL-13 (1)(2)(3)(4), the latter of which may underlie some of the polygenic component of allergic asthma associated with elevated IgE. Second, allergic asthma is associated with two distinct phases of bronchoconstriction: an immediate phase on antigen exposure that depends on mast cell-derived mediators and a late phase bronchoconstriction occurring hours after antigen exposure that is associated with accumulation of eosinophils and TH2 lymphocytes in the airways (5,6).…”