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Am J Physiol Lung Cell Mol Physiol 292: L1564-L1571, 2007. First published March 9, 2007; doi:10.1152/ajplung.00273.2006
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Dose-dependent recruitment of CD25+ and CD26+ T cells in a novel F344 rat model of asthma

Thomas Skripuletz,1 Andreas Schmiedl,1 Jutta Schade,1 Sammy Bedoui,1,2 Thomas Glaab,3 Reinhard Pabst,1 Stephan von Hörsten,1,4 and Michael Stephan1

1Department of Functional and Applied Anatomy, Medical School of Hannover, Germany; 2Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; 3Department of Respiratory Medicine, Medical School of Hannover, Germany; and 4Experimental Therapy, Franz-Penzoldt-Center, Friedrich-Alexander-University, Erlangen, Germany

Submitted 20 July 2006 ; accepted in final form 4 March 2007

The ovalbumin (OVA)-induced airway inflammation in rats is a commonly used model to explore the pathobiology of asthma. However, its susceptibility varies greatly between rat strains, and presently Brown Norway (BN) rats are preferentially used. Since recruitment of T cells to the lungs depends on the CD26 (dipeptidyl peptidase IV, DPPIV) expression, Fischer 344 strain (F344) rats are a highly relevant rat strain, in particular because CD26-deficient substrains are available. To establish a F344 rat model of asthma, we challenged F344 rats using different doses of aerosolized antigen (0%, 1%, 2.5%, 5%, and 7.5% OVA) and compared these effects with intratracheal instillation of OVA (1.5 mg/0.3 ml). Asthmoid responsiveness was determined by analysis of early airway responsiveness (EAR), antigen-specific IgE levels, as well as airway inflammation including the composition of T cell subpopulations in the bronchoalveolar lavage (BAL) and lung tissue with special respect to the T cell activation markers CD25 and CD26. Even low allergen doses caused allergen-specific EAR and increases of antigen-specific IgE levels. However, EAR and IgE levels did not increase dose dependently. Higher concentrations of OVA led to a dose-dependent increase of several immunological markers of allergic asthma including an influx of eosinophils, T cells, and dendritic cells. Interestingly, a dose-dependent increase of CD4+/CD25+/CD26+ T cells was found in the lungs. Summarizing, we established a novel F344 rat model of aerosolized OVA-induced asthma. Thereby, we found a dose-dependent recruitment of cellular markers of allergic asthma including the activated CD4+/CD25+/CD26+ T cell subpopulation, which has not been described in asthma yet.

ovalbumin; dipeptidyl-peptidase IV; animal; regulatory T cells



Address for reprint requests and other correspondence: M. Stephan, Functional und Applied Anatomy -4120-, Medical School of Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany (e-mail: Stephan.Michael{at}mh-hannover.de)




This article has been cited by other articles:


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J. Histochem. Cytochem.Home page
J. Schade, M. Stephan, A. Schmiedl, L. Wagner, A. J. Niestroj, H.-U. Demuth, N. Frerker, C. Klemann, K. A. Raber, R. Pabst, et al.
Regulation of Expression and Function of Dipeptidyl Peptidase 4 (DP4), DP8/9, and DP10 in Allergic Responses of the Lung in Rats
J. Histochem. Cytochem., February 1, 2008; 56(2): 147 - 155.
[Abstract] [Full Text] [PDF]




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