Phenotype and functional properties of bronchoalveolar T cells from asthmatic and normal lungs

Bodey, Kathleen Jane (2004) Phenotype and functional properties of bronchoalveolar T cells from asthmatic and normal lungs. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

To further investigate the role of lung T cells in atopic asthma, T cells were isolated from BAL and peripheral blood (PB) of atopic asthmatics and healthy normal control subjects and their capacity to proliferate in respond to non-specific mitogens and specific allergens in vitro were examined. Enrichment of lymphocytes from BAL resulted in obtaining viable populations of alveolar lymphocytes of the CD4⁺CD45RO⁺ and CD8⁺CD45RO⁺ phenotype that have been primed and exhibit the memory cell function. There was no significant difference between asthmatics and normal control subjects in the proliferative responses to any of the stimuli used on either BP- or BAL-derived T cells. However, whereas the responses of cells from blood were significantly higher than those from BAL in normal control subjects, no such differences was seen when blood and BAL cells from asthmatic subjects were compared. The responsiveness of airway T lymphocytes appears not to be dependent upon IL-2 as a growth factor or the suppressive function of macrophages but may be enhanced because of a defective function of airways CD8⁺ T lymphocytes, or may be due to a defect in the response of regulatory T cells in asthma.

Using a model of local allergen challenge, the cytokine profiles of T cells from asthmatic airways before and after local allergen challenge were examined. The results showed basal expression of TNFα, IFNγ, IL-13, IL-6 and GM-CSF in both the saline and allergen challenged BAL T cells taken 10 minutes after challenge. BAL T cells from 24 hour post challenge lavage showed increased expression of IL-13, IL-4, IL-3 and IL-5 with less IFNγ. Stimulation of the BAL T cells from saline site with PHA showed increased expression of IL-13, IL-4, IL-3 and IL-5, but not when stimulated with HDM. Resting T cells in the asthmatic airways express an intermediate cytokine profile with IL-13 and IFNγ prominent, but type 2 cytokines are markedly upregulated after local allergen challenge.

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