CD26 (dipeptidyl-peptidase IV)-dependent recruitment of T cells in a rat asthma model.
CD26 truncates several chemokines as well as neuropeptides and influences immune responses via modulation of cell adhesion and T cell activation, suggesting an involvement of CD26 in asthmatic and airway inflammation. Therefore, Fischer 344 (F344), Brown Norway (BN) and Lewis (LEW) rat strains, which differ in their CD26-like enzymatic activity, were compared using an asthma model. Additionally, two CD26-deficient mutant F344 rat substrains were included and compared to the wild-type F344 substrain. Immunization was performed twice with ovalbumin (OVA), and 2 weeks later the rats were challenged with OVA intratracheally Flow cytometry (FACS) analysis of different leucocyte subsets as well as enzyme-linked immunosorbent assay (ELISA) for IgE levels in the blood and bronchoalveolar lavage (BAL) were performed 24 h after challenge. LEW rats with the lowest CD26 activity among the rat strains investigated here displayed significantly reduced CD4+ T cell numbers in the BAL compared to wild-type F344 and BN rats. Moreover, in asthma, the ratio of CD26+ to CD26- T cell receptor (TCR)-positive cells increased significantly in F344 and LEW but not BN rats. Most intriguingly, in both CD26-deficient F344 rat substrains the number of CD4+ T lymphocytes was markedly reduced compared to wild-type F344. The decrease in T cell recruitment observed in the CD26-deficient rats was associated with significantly reduced OVA-specific IgE-titres. This is the first report to show a remarkably reduced T cell recruitment in rat strains that either lack or exhibit reduced CD26-like enzymatic activity, suggesting a role for CD26 in the pathogenesis of asthma via T cell-dependent processes such as antibody production.
Kruschinski
C
C
Department of Functional and Applied Anatomy, Medical School of Hannover, Hannover, Germany.
Skripuletz
T
T
Bedoui
S
S
Tschernig
T
T
Pabst
R
R
Nassenstein
C
C
Braun
A
A
von Hörsten
S
S
D000818:Animals; D001249:Asthma / Q000097:blood / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D007073:Immunoglobulin E; D010047:Ovalbumin; D018819:Dipeptidyl Peptidase 4