T cell inflammatory response, Foxp3 and TNFRS18-L regulation of peripheral blood mononuclear cells from patients with nasal polyps-asthma after staphylococcal superantigen stimulation

Pérez-Novo, C.A.; Jedrzejczak-Czechowicz, M.; Lewandowska-Polak, A.; Claeys, C.; Holtappels, G.; Van Cauwenberge, P.; Kowalski, M.L.; Bachert, C.

doi:10.1111/J.1365-2222.2010.03577.X

Title

T cell inflammatory response, Foxp3 and TNFRS18-L regulation of peripheral blood mononuclear cells from patients with nasal polyps-asthma after staphylococcal superantigen stimulation

Author

Pérez-Novo, C.A.

Jedrzejczak-Czechowicz, M.

Lewandowska-Polak, A.

Claeys, C.

Holtappels, G.

Van Cauwenberge, P.

Kowalski, M.L.

Bachert, C.

Abstract

BACKGROUND Staphylococcal superantigens may modulate airway inflammatory disease. OBJECTIVE We assessed the effect of Staphylococcus aureus enterotoxin B (SEB) on T cell activation in patients with nasal polyps and asthma, and its possible link to aspirin hypersensitivity. METHODS Leucocytes were isolated from five healthy subjects (controls), five asthmatics with nasal polyps without (NP-ATA) and five with aspirin-induced asthma (NP-AIA). Cells were incubated with increasing concentrations of SEB for 4 and 18 h. Release of T(H)1/T(H)2 cytokines was assessed by Cytometric Bead-Array. Foxp3 and TNFRS18-L expression were analysed by qPCR and flow cytometry. RESULTS After 4 and 18 h, SEB significantly increased IFN-gamma, IL-4, TNF-alpha, IL-5 and IL-2 concentrations in supernatants of both NP polyp groups compared with controls. Baseline Foxp3 was significantly decreased in both NP-asthma groups. Incubation with SEB for 4 h induced a limited up-regulation of Foxp3 in NP-AIA patients, which was switched off consecutively. Foxp3 was significantly up-regulated in the control group after 18 h, but not in the NP-asthmatic groups. In parallel, TNFRS18-L mRNA significantly increased after 18 h in the NP-asthma groups compared with control subjects. This molecule was highly expressed in CD11c(+)CD14(+) cells and its levels increased after 18 and 24 h culture in the NP-asthma patients. CONCLUSION SEB induces both T(H)1 and T(H)2 pro-inflammatory responses in patients with nasal polyps and asthma regardless of the presence of aspirin hypersensitivity. The nature of this response may be linked to a basal deficiency of Foxp3 observed in the NP-asthmatic patients and/or to the up-regulation of TNFRS18-L on monocytes/dendritic cell precursors.

Language

English

Source (journal)

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

Publication

2010

DOI

10.1111/J.1365-2222.2010.03577.X

Volume/pages

40 :9 (2010) , p. 1323-1332

ISI

000280651700006