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

Abstract

ABSTRACT. Hypothesis. Activated CD8 as well as CD4 T cells contribute to the production of asthma-relevant cytokines in both atopic and nonatopic childhood asthma.Objectives. To measure the percentages of peripheral blood CD4 and CD8 T cells expressing naïve/memory (CD45RA/CD45RO) and activation (HLA-DR, CD25) markers, as well as mRNA-encoding interleukin-4 (IL-4) and interleukin-5 (IL-5) in atopic and nonatopic childhood asthmatics and in nonasthmatic controls matched for age and atopic status; and to study the effects of inhaled glucocorticoid therapy of the asthmatics on these measurements.Methods. Peripheral blood mononuclear cells were isolated from 17 atopic and 8 nonatopic stable (not acutely ill) asthmatics aged 7 to 16 years with moderateto-severe disease and from 15 nonasthmatic controls matched for age and atopic status. Activation markers on CD4 and CD8 T cells were measured by flow cytometry, and expression of cytokine mRNA by in situ hybridization with CD4 and CD8 T cells were isolated using magnetic beads. Measurements were repeated in 18 of the asthmatics 4 to 6 months after initiation or escalation of inhaled glucocorticoid therapy for inadequately controlled asthma.Results. The percentages of CD4 T cells expressing CD45RO but not CD45RA were elevated in both asthma groups as compared with the relevant controls and were reduced in association with de novo or augmented inhaled glucocorticoid therapy. The percentages of CD8 T cells expressing both markers were not elevated in asthmatics as compared with controls. The percentages of both CD4 and CD8 T lymphocytes expressing HLA-DR and CD25 were elevated in the asthmatics as compared with controls, and significantly reduced in association with de novo or augmented inhaled glucocorticoid therapy. ABBREVIATIONS. IL-5, interleukin 5; IL-4, interleukin 4; IgE, immunoglobulin E; FEV1, forced expiratory volume in 1 second; PEF, peak expiratory flow; FITC, fluoroscein isothiocyanate; PE, phycoerythrin; PBS, phosphate-buffered saline; NK, natural killer.

T-helper cell type-2 regulation in allergic disease

“…In some studies this apparent Th2 bias in asthma extends outside of the airway to circulating lymphocytes [33][34][35]. Furthermore, research in mouse models has established the critical roles that Th2 cytokines play in the pathophysiology of asthma, including mucus hypersecretion and AHR [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50], and a recent study emphasised the importance of IL-4 and IL-13 in airway dysfunction and remodelling in response to chronic allergen exposure [50].…”

Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma

“…[11][12][13][14] Likewise, inhaled glucocorticoid treatment has been shown to reduce activation of peripheral T cells, as well as IL-4 and IL-5 expression. 15 However, it is currently unknown how glucocorticoid treatment affects the activity or frequency of T reg cells.…”

Intracellular production of IL-2, IL-4, IFN-γ, and TNF-α by peripheral blood CD3+ and CD4+ T cells in children with atopic dermatitis

“…[12,39]. One study documented the modulating effect of ICS also on PBMC cytokine expression [11]. In addition, corticosteroids increase IL-10 production by T cells and macrophages, which may lead to a decrease in TNF-α synthesis.…”