Dose-dependent recruitment of CD25+ and CD26+ T cells in a novel F344 rat model of asthma.
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.
Skripuletz
Thomas
T
Department of Functional and Applied Anatomy, Medical School of Hannover, Germany.
Schmiedl
Andreas
A
Schade
Jutta
J
Bedoui
Sammy
S
Glaab
Thomas
T
Pabst
Reinhard
R
von Hörsten
Stephan
S
Stephan
Michael
M
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016084:Bronchoconstriction / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D053645:Interleukin-2 Receptor alpha Subunit; D007073:Immunoglobulin E; D010047:Ovalbumin; D018819:Dipeptidyl Peptidase 4