Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/9545
Title: T lymphocyte Recruitment to the Lung in Asthma
Authors: Mutalithas, Kugathasan
Supervisors: Wardlaw, Andrew
Guillen, Cristina
Award date: 3-Jul-2009
Presented at: University of Leicester
Abstract: T cells play an important part in the pathogenesis of asthma. In this study greater numbers of T cells were seen in the bronchial epithelium of severe asthmatics compared to normal subjects. There were greater percentages of both IL-4+ and IFN-γ+ T cells in the bronchoalveolar lavage of asthmatics compared to normal subjects. Chemokines and their receptors are thought to act as signals that guide particular subsets of T cells to the lung in asthma. Using flow cytometry I had explored whether the chemokine receptors CCR8 and CRTh2 played any role in recruiting T cells and in particular IL-4+ T cells to the lung in asthma. Both receptors selectively identified IL-4+ and IL-13+ T cells in the blood and bronchoalveolar lavage from asthmatics and normal subjects. Cells expressing CCR8 but not CRTh2 were found at a higher percentage in the blood of severe asthmatics compared to normal controls. The percentage of CCR8+ T in the bronchoalveolar lavage of asthmatics was higher compared to normal subjects and furthermore, there was a greater percentage of CCR8+ T cells in the bronchoalveolar lavage compared to blood within the same asthmatic subject. This difference in the percentage of CCR8+ T cells between blood and BAL was not seen in normal subjects. This suggests that there may be a role for CCR8 in the recruitment of T cells to the lung in asthma. In support of this, higher concentrations of the ligand CCL1, were seen in the bronchoalveolar lavage of asthmatics compared to that from normal subjects. Little experimental evidence was found that supported the contention that CRTh2 played a significant role in T cell recruitment to the lung. As a marker of IL-4+ T cells in asthmatics, CCR8 compared favourably with CRTh2 as they identified a greater percentage of IL-4+ T cells in bronchoalveolar lavage than CRTh2. CCR8 also compared favourably with CCR4 as a marker for IL-4+ T cells due to higher specificity. The iNKT subset of T cells has been claimed to be an important group of T cells in asthma and was reported to be present at high percentages in the lung of moderate to severe asthmatics. In this study we had shown that in asthmatics these cells are present in very low percentages, similar to that in normal subjects and that they probably do not play a significant role in severe asthma.
Links: http://hdl.handle.net/2381/9545
Type: Thesis
Level: Doctoral
Qualification: MD
Appears in Collections:Theses, Dept. of Infection, Immunity and Inflammation
Leicester Theses

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