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An investigation of the impact of the location and timing of antigen-specific t cell division on airways inflammation

Hutchison, S. and Choo-Kang, B.S.W. and Gibson, V.B. and Bundick, R.V. and Leishman, A.J. and Brewer, J.M. and McInnes, I.B. and Garside, P. (2009) An investigation of the impact of the location and timing of antigen-specific t cell division on airways inflammation. Clinical and Experimental Immunology, 155 (1). pp. 107-116. ISSN 0009-9104

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Abstract

It is widely accepted that allergic asthma is orchestrated by T helper type 2 lymphocytes specific for inhaled allergen. However, it remains unclear where and when T cell activation and division occurs after allergen challenge, and whether these factors have a significant impact on airways inflammation. We therefore employed a CD4-T cell receptor transgenic adoptive transfer model in conjunction with laser scanning cytometry to characterize the location and timing of T cell division in asthma in vivo. Thus, for the first time we have directly assessed the division of antigen-specific T cells in situ. We found that accumulation of divided antigen-specific T cells in the lungs appeared to occur in two waves. The first very early wave was apparent before dividing T cells could be detected in the lymph node (LN) and coincided with neutrophil influx. The second wave of divided T cells accumulating in lung followed the appearance of these cells in LN and coincided with peak eosinophilia. Furthermore, accumulation of antigen-specific T cells in the draining LN and lung tissue, together with accompanying pathology, was reduced by intervention with the sphingosine 1-phosphate receptor agonist FTY720 2 days after challenge. These findings provide greater insight into the timing and location of antigen-specific T cell division in airways inflammation, indicate that distinct phases and locations of antigen presentation may be associated with different aspects of pathology and that therapeutics targeted against leukocyte migration may be useful in these conditions.

Item type: Article
ID code: 19416
Keywords: asthma, immune regulation, T cells, Pharmacy and materia medica, Immunology, Immunology and Allergy
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 19 May 2010 15:02
    Last modified: 05 Sep 2014 03:07
    URI: http://strathprints.strath.ac.uk/id/eprint/19416

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