T cells expressing the γδ receptor are essential for Th2‐mediated inflammation in patients with acute exacerbation of asthma

Abstract

OBJECTIVE: T lymphocytes have a central regulatory role in the pathogenesis of asthma. The objective of this study was to characterize immunologically the activation stage of asthma and the functional profile of lymphocytes from induced sputum, with particular emphasis on gammadelta T cells. METHODS: Induced sputum was collected from 10 patients with acute exacerbation of asthma, and from healthy controls. The expression of activation markers on freshly isolated induced sputum lymphocytes and T-cell subsets was analyzed by double immunofluorescent staining and flow cytometry. Fas ligand (FasL) was determined by reverse transcriptase-polymerase chain reaction analysis. The phenotype of gammadelta T-cell subpopulations was tested by A13 and BB3 monoclonal antibodies. In this context, the functional profile of gammadelta T cells was tested in a chromium releasing test. RESULTS: A significantly decreased proportion of alphabeta T cells and an increased proportion of gammadelta T cells, CD56+ cells and CD8+ gammadelta T cells were found in asthma patients compared with healthy controls. In asthmatic patients, there is a significantly increased proportion of T cells expressing CD69 and CD25 antigen. After stimulation of gammadelta T cells, an increased expression of intracellular tumour necrosis factor-alpha, interleukin (IL)-4 and IL10 cytokines were found at higher levels than controls. Interferon-gamma was observed at similar levels in asthma patients and healthy controls. Freshly isolated T-cell receptor (TCR) gammadelta+ cells exhibited an increased percentage of FasL in our patient group. FasL mRNA was detected in TCR gammadelta+ cells before and after IL2 stimulation. TCR gammadelta+ cells were cytotoxic against the K562 cell line. This natural killer activity was mediated by the A13-positive subpopulation. CONCLUSION: The presence of cytokines producing gammadelta cells in induced sputum of asthmatic patients is consistent with regulatory activities. These cells display also cytotoxic function.

Reduced bronchial CD4+ T-cell density in smokers with occupational asthma

“…It is debated whether cd-T-cells protect the bronchial mucosa or promote airway inflammation [22]. While increased cd-T-cell counts have been reported in bronchoalveolar lavage [23] and induced sputum from asthmatics with acute exacerbations [24], other studies report no difference between asthmatic and control subjects in bronchial biopsies [25] and bronchoalveolar lavage [22,26]. The current observation of depleted intraepithelial cd-T-cell levels in asthmatics supports the theory that these cells are involved in maintaining mucosal homeostasis.…”

γδT cells suppress inflammation and disease during rhinovirus-induced asthma exacerbations

“…6, 7 γδT cells, in particular, possess a range of functions that might make them key players in inflammatory airways diseases such as asthma, including maintenance of epithelial tissue homeostasis, 8, 9 modulation of innate and adaptive immune responses, 10, 11, 12 and the ability to contribute to respiratory pathogen control. 13, 14 γδT cells are reportedly enriched in asthmatic airways 15, 16, 17 and, in mouse studies, have been shown to influence AHR and/or airways inflammation in acute and chronic allergic asthma models. 18, 19, 20 However, because differing effects on AHR and allergic inflammation have been described depending on the model, method, timing, or subset of γδT cells manipulated, their function in asthma pathogenesis remains somewhat ambiguous.…”

Asthma

“…The antigenic molecules that activate γδ T cells are still largely unknown. As might be expected γδ T cells are elevated in the BAL fluid of asthmatics (Molfino et al, 1996) and in induced sputum (Hamzaoui et al, 2002); however, their exact functions in the disease have yet to be elucidated. Furthermore, γδ T cells have a prominent role in the recognition of lipid antigens (Paget et al, 2012) and may be activated by heat-shock proteins (Hirsh and Junger, 2008).…”